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Background: Stroke is a major cause of premature mortality in Britain, but its burden is markedly greater amongst South Asians. Because of the paucity of data in this area, we investigated the magnitude and impact of risk from cardiovascular comorbidities on survival amongst South Asian stroke patients. Methods: We reviewed hospital case records of consecutive first in life time ischaemic stroke patients [self reported ethnicity and International Classification of Disease (ICD) 10th revision, codes 430-438] admitted to an inner city hospital in the UK between 1997 and 2001. In-hospital mortality data and CVD risk factors were analysed. Five-year mortality data was obtained from the National Health Tracing Services. Results: Of 1474 ischaemic stroke patients, 242 (16%) were South Asian of whom, 143 (59.1%) were male. The prevalence of hypertension was 70.2%, followed by diabetes 56.2%, hyperlipidaemia 7% and myocardial infarction 10.3%. At 5 years follow-up, 40.5% had died. Cumulative event-free survival at 5 years was significantly poorer in patients with diabetes (log-rank test, p = 0.009). On Cox regression analysis, incorporating age, gender and other CVD risk factors, diabetes mellitus was an independent predictor of mortality odds ratio = 1.65 (1.02-2.6, p = 0.039). Hypertension and dyslipidaemia did not discriminate survival amongst South Asian patients. Conclusion: Stroke mortality in South Asians is associated with presence of diabetes mellitus. This highlights the significance of early and intensive CVD risk modification strategies in ethnic minorities particularly in patients with diabetes. Further research is warranted in South Asians to examine the underlying basis and related pathophysiological abnormalities. [ABSTRACT FROM AUTHOR]

It is increasingly accepted that more intensive lipid-lowering treatment is associated with greater cardiovascular risk reductions in patients with coronary heart disease (CHD), thus providing a rationale for more aggressive LDL-cholesterol (LDL-C) targets. Ezetimibe in combination with statin therapy provides an additional approach to lipid management by utilising the additive action of two different mechanisms of LDL-C reduction. In this multicentre, randomised, double-blind, placebo-controlled study, a total of 98 men and 55 women with CHD and primary hypercholesterolaemia, naïve to statin therapy, were randomised to receive treatment for 6 weeks with either ezetimibe 10 mg-simvastatin 20 mg ( n = 77) or placebo-simvastatin 20 mg ( n = 75). At 6 weeks, ezetimibe 10 mg-simvastatin 20 mg provided a mean additional LDL-C reduction of 14.6% (95% CI 10.1-19.1) compared with simvastatin monotherapy (p < 0.0001). Moreover, a higher proportion of patients on ezetimibe/simvastatin achieved the National Standard Framework LDL-C standard (<3.0 mmol/l; 93% vs. 75%, p < 0.001) or the new Joint British Societies (JBS 2) goal of LDL-C < 2.0 mmol/l (49.3% vs. 11.1%, p < 0.001). On logistic regression analysis, the odds ratio of achieving target LDL-C with ezetimibe 10 mg-simvastatin 20 mg was 5.1 (95% CI 1.8-15.0) times higher than with simvastatin monotherapy (p = 0.003). Clinical chemistry profiles and proportions of adverse events were similar in both groups at baseline and follow-up. In conclusion, ezetimibe 10 mg-simvastatin 20 mg is a practical, effective and safe option for the treatment of primary hypercholesterolaemia in CHD patients, and brings more patients to new aggressive cholesterol targets compared with simvastatin 20 mg monotherapy. [ABSTRACT FROM AUTHOR]

Objective: The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial enrolled participants with chronic limb threatening ischaemia who required an infrapopliteal, with or without a femoropopliteal, revascularisation procedure to restore limb perfusion. Participants randomised to a vein bypass (VB) first revascularisation strategy were over one third more likely than those randomised to a best endovascular treatment (BET) first revascularisation strategy to die from any cause during a median follow up of 40.0 (interquartile range 20.9, 60.6) months. The aim of the present study was to describe the timing and causes of death in BASIL-2 as a first step towards trying to better understand why randomisation to a VB first revascularisation strategy was associated with this excess mortality., Methods: A 10 person international panel comprising vascular and endovascular surgeons as well as vascular interventional radiologists, who had all been principal investigators in BASIL-2, took part in a modified Delphi consensus exercise to adjudicate the primary cause of death and, in particular, whether the cause was primarily cardiac or non-cardiac., Results: In 151 of 168 deaths (89.9%), the Delphi panel achieved a consensus regarding the cause of death being probably cardiac or non-cardiac. In the BET group, 16 of 77 deaths (21%) were classified as probably cardiac compared with 32 of 91 (35%) in the VB group (unadjusted subdistribution hazard ratio 2.16, 95% confidence interval [CI] 1.20 - 3.87; unadjusted cause specific hazard ratio 2.15, 95% CI 1.19 - 3.90). At the point of randomisation, 64 of 344 (18.6%), 40 of 342 (11.7%), and 37 of 344 (10.8%) participants had a previous myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG), respectively. There was no evidence of varying treatment effects for cause of death in subgroup analyses of previous PCI, CABG, or MI., Conclusion: The excess mortality observed in the VB first revascularisation strategy group in BASIL-2 was largely due to deaths that were adjudicated by the Delphi panel as probably primarily cardiac. These excess cardiac deaths were observed throughout follow up and there was no evidence of non-proportional hazards. Further work is ongoing to try to better understand the reasons for these findings., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To study the use of medial sural artery perforator (MSAP) free flap in head and neck reconstruction., Material and Method: This was a prospective study. The patients with cancers of head and neck underwent excision of tumor along with neck dissection, and MSAP free flap was used for reconstruction., Results: The free MSAP flaps were used in 30 patients to reconstruct head and neck soft tissue defects. There were sixteen male and six female patients with the median age of 40 years. The most common site of tumor resection was the tongue (14 cases), followed by buccal mucosa (12 cases), neck skin(2 cases), skin over parotid(1 case) and lip(1 case). Average flap size was 56 cm 2 . Thickness of the flap ranged from 4 to 8 mm. The length of the vascular pedicle ranged from 8 to 14 cm (12 cm mean) which provides sufficient length during vessel anastomosis. Arterial diameter ranged from 1.0 to 1.5 mm(Average - 1.25 mm) and venous diameter of both veins in pedicle ranged from 1.5 to 2.5 mm(Average - 2 mm) in size. Most flaps were based on two perforators. Primary closure was attained in 11 cases whereas 19 patients required split thickness skin graft(STSG). The average flap harvesting time was 45 min. Flap was failed in two cases., Conclusion: MSAP is good alternative to FRAFF in the reconstruction of defect after resection of head and neck cancer., Competing Interests: Disclosure of Potential Conflicts of InterestThere is no conflict of interest of any of author., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Extensive composite defects involving the lip and cheek present difficult reconstructive challenges in view of functional recovery like oral competence, articulation, speech and mastication. This study presents our results of reconstructing through and through cheek defect with the use of free anterolateral thigh (ALT) flaps. All the patients with carcinoma of buccal mucosa and cheek who underwent through and through cheek resection and reconstructed with free composite pedalled anterolateral thigh flap between March 2019 to March 2020 were included in the study. We have assessed the post-operative functional outcome using University of Washington Quality of Life Questionnaire at the end of 12 months duration. We have excluded lost to follow-up and flap failure patients. Fifty patients were matched our inclusion criteria. Mean age was 43 years. Male to female ratio was 4.6:1. Stage 3 disease was in 8 patients and stage 4 disease was in 42 patients. Average size of the flap required was 15 × 7.5 cm, maximum was 24 × 11 cm. Oral competence was good in 74% patients. 80% patients were able to take semisolid diet, 8% were on liquid diet and 12% were dependent on RT feed. Average physical function (70.47 ± 19.09), social-emotional sub-score (81.72 ± 16.63) and composite scores (76.09 ± 17.86) were good and within acceptable range. Chewing (53 ± 29.29) and swallowing (64 ± 21.57) scored poorly among 12 domains. For extensive through and through cheek defects bipedelled ALT provides good functional outcome. In view of advance disease status extensive resection would be responsible for bone and mucosal loss affecting chewing and swallowing., Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03416-3., Competing Interests: Conflict of interestThere is no conflict of interest of any of author., (© Association of Otolaryngologists of India 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion., Methods: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689., Findings: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive)., Interpretation: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy., Funding: UK National Institute of Health Research Health Technology Programme., Competing Interests: Declaration of interests AWB reports salary part paid by a National Institute for Health (NIHR) and Care Research Health Technology Assessment (HTA) BASIL-2 grant; payment expert advice and testimony from NHS Resolution, His Majesty's Coroners, National Crime Agency, UK, Scotland, Wales, and Northern Ireland Governments, and various law firms, outside of the submitted work; and payment to his institution and personal honoraria for committee work from NIHR HTA and NICE. GRB reports salary part paid by a NIHR HTA BASIL-2 grant; the BASIL-2 grant also paid mileage for visiting patients in the BASIL-2 trial for follow-up assessments. AD reports honoraria from Boston Scientific, Cordis, Medalliance, and Abbott. KH reports honoraria from Le Maitre and Bayer. STR reports payment for expert testimony from McCollum Consultants; consulting fees from 3M, Bayer, and Avita; speaker fees from 3M, Bayer, Avita, and Terumo; travel support Bayer and Terumo; and is an advisory board member for 3M, Bayer, and Avita. AS reports honoraria and institutional grant support from Shockwave and Abbott and unpaid committee work for NICE. HZ reports an institutional grant from Abbott and honoraria from Limflow, Abbott, Boston Scientific, Bentley, Cook Medical, and Medtronic. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Through and through complex oro-mandibular defect usually involves buccal mucosa, mandibular segment, lip, and outer cheek skin. Reconstruction of such extensive three-dimensional defects pose a great challenge to reconstructive surgeons which requires use of two flaps. There are diverse options for such types of defects like use two pedicled flaps, one free flap, one pedicled flap or use of two free flaps. Amongst them the use of dual free flaps is ideal for the reconstruction. Commonly used dual free flaps are free fibula osteocutaneous flap for mandible, buccal mucosal defect and free radial artery flap or antero-lateral flap for cheek defect. The major disadvantages of using these two free flaps include two different sites for flap harvest, more time for harvesting and increased overall surgery time. We present our experience of reconstruction of large oro-mandibular defect using free osteo-cutaneous fibula flap and lateral sural artery free flap from single limb in six patients between January 2019 and December 2020. Minimum follow up was 6 months., Competing Interests: Conflict of interestThere is no conflict of interest of any of author., (© Association of Otolaryngologists of India 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: Since the approval of cyclin-dependent kinase 4/6 inhibitors in 2015, this oral cancer (OC) therapy has been combined with oral endocrine therapy as first-line treatment in metastatic hormone receptor-positive breast cancer, adding unique toxicity and complexity to the successful administration of this oral medication. Implementation of OC is challenging because of delays in treatment and nonadherence and is worse among vulnerable patient populations. Pharmacists may mitigate these barriers with facilitation of prior authorizations, communication with pharmacies, toxicity management, adherence counseling, and optimization of dosing schedules and regimens., Materials and Methods: We conducted a quality improvement project to decrease the average number of treatment day delays during the first six cycles of OC. Patients were enrolled on the OPTIMAL protocol, a high-touch pharmacy intervention incorporating pharmacists within outpatient oncology clinic visits with the providers. Pharmacists met with patients, identified individual barriers to treatment, and performed counseling including toxicity and adherence assessments., Results: A preintervention assessment identified an average treatment day delay of 7.7 (range, 3.2-15.3) days during the first six cycles of OC. During the intervention period, 53 patients were enrolled on the OPTIMAL protocol and experienced an average treatment day delay of 2.1 (0.6-4) days, P < .0001. Delays were characterized as modifiable and unmodifiable. Pharmacists documented 640 interventions, including medication reconciliations and clinical recommendations. Forty-two patients reported treatment-related toxicities, resulting in 33 therapy and 20 dose modifications., Conclusion: Our initiative to incorporate pharmacists in clinic visits at an outpatient breast cancer clinic was associated with decreased treatment day delays during the first six cycles of treatment. Pharmacists performed a multitude of meaningful interventions to facilitate treatment in a particularly vulnerable population and play a valuable role in comanaging patients.

Introduction: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?', Methods and Analysis: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years., Ethics and Dissemination: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences., Trial Registration Number: ISRCTN85731188., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Acute limb ischaemia usually is caused by a blood clot blocking an artery or a bypass graft. Severe acute ischaemia will lead to irreversible damage to muscles and nerves if blood flow is not restored in a few hours. Once irreversible damage occurs, amputation will be necessary and the condition can be life-threatening. Infusion of clot-busting drugs (thrombolysis) is a useful tool in the management of acute limb ischaemia. Fibrinolytic drugs are used to disperse blood clots (thrombi) to clear arterial occlusion and restore blood flow. Thrombolysis is less invasive than surgery. A variety of techniques are used to deliver fibrinolytic agents. This is an update of a review first published in 2004., Objectives: To compare the effects of infusion techniques during peripheral arterial thrombolysis for treatment of patients with acute limb ischaemia., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 20 October 2020. We undertook reference checking to identify additional studies., Selection Criteria: We included all randomised controlled trials (RCTs) comparing infusion techniques for fibrinolytic agents in the treatment of acute limb ischaemia., Data Collection and Analysis: We used standard methodological procedures as recommended by Cochrane. We assessed the risk of bias in included trials using the Cochrane 'Risk of bias' tool. We evaluated certainty of evidence using GRADE. For dichotomous outcomes, we calculated the odds ratio (OR) with the corresponding 95% confidence interval (CI). We were not able to carry out meta-analyses due to clinical heterogeneity, so we have reported the results and performed the comparisons narratively. The main outcomes of interest were amputation-free survival or limb salvage, amputation, mortality, vessel patency, duration of thrombolysis, and complications such as cerebrovascular accident and major and minor bleeding., Main Results: Nine studies with a total of 671 participants are included in this update. Trials covered a variety of infusion techniques, dosage regimens, and adjunctive agents. We grouped trials according to types of techniques assessed (e.g. intravenous and intra-arterial delivery of the agent, 'high-' and 'low-dose' regimens of the agent, continuous infusion and 'forced infusion' of the agent, use of adjunctive antiplatelet agents). We assessed the certainty of evidence as very low to low due to the limited power of individual studies to deliver clinically relevant results, small and heterogeneous study populations, use of different inclusion criteria by each study in terms of severity and duration of ischaemia, considerably different outcome measures between trials, and use of different fibrinolytic agents. This heterogeneity prevented pooling of data in meta-analyses. No regimen has been shown to confer benefit in terms of amputation-free survival (at 30 days), amputation, or death. For vessel patency, complete success was more likely with intra-arterial (IA) than with intravenous (IV) infusion (odds ratio (OR) 13.22, 95% confidence interval (CI) 2.79 to 62.67; 1 study, 40 participants; low-certainty evidence); radiological failure may be more likely with IV infusion (OR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants; low-certainty evidence). Due to the small numbers involved in each arm and design differences between arms, it is not possible to conclude whether any technique offered any advantage over another. None of the treatment strategies clearly affected complications such as cerebrovascular accident or major bleeding requiring surgery or blood transfusion. Minor bleeding complications were more frequent in systemic (intravenous) therapy compared to intra-arterial infusion (OR 0.03, 95% CI 0.00 to 0.56; 1 study, 40 participants), and in high-dose compared to low-dose therapy (OR 0.11, 95% CI 0.01 to 0.96; 1 study, 63 participants). Limited evidence from individual trials appears to indicate that high-dose and forced-infusion regimens reduce the duration of thrombolysis. In one trial, the median duration of infusion was 4 hours (range 0.25 to 46) for the high-dose group and 20 hours (range 2 to 46) for the low-dose group. In a second trial, treatment using pulse spray was continued for a median of 120 minutes (range 40 to 310) compared with low-dose infusion for a median of 25 hours (range 2 to 60). In a third trial, the median duration of therapy was reduced with pulse spray at 195 minutes (range 90 to 1260 minutes) compared to continuous infusion at 1390 minutes (range 300 to 2400 minutes). However, none of the studies individually showed improvement in limb salvage at 30 days nor benefit for the amputation rate related to the technique of drug delivery. Similarly, no studies reported a clear difference in occurrence of cerebrovascular accident or major bleeding. Although 'high-dose' and 'forced-infusion' techniques achieved vessel patency in less time than 'low-dose' infusion, more minor bleeding complications may be associated (OR 0.11, 95% CI 0.01 to 0.96; 1 study, 72 participants; and OR 0.48, 95% CI 0.17 to 1.32; 1 study, 121 participants, respectively). Use of adjunctive platelet glycoprotein IIb/IIIa antagonists did not improve outcomes, and results were limited by inclusion of participants with non-limb-threatening ischaemia., Authors' Conclusions: There is insufficient evidence to show that any thrombolytic regimen provides a benefit over any other in terms of amputation-free survival, amputation, or 30-day mortality. The rate of CVA or major bleeding requiring surgery or blood transfusion did not clearly differ between regimens but may occur more frequently in high dose and IV regimens. This evidence was limited and of very low certainty. Minor bleeding may be more common with high-dose and IV regimens. In this context, thrombolysis may be an acceptable therapy for patients with marginally threatened limbs (Rutherford grade IIa) compared with surgery. Caution is advised for patients who do not have limb-threatening ischaemia (Rutherford grade I) because of risks of major haemorrhage, cerebrovascular accident, and death from thrombolysis., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The isotropic metaphase actin cortex progressively polarizes as the anaphase spindle elongates during mitotic exit. This involves the loss of actomyosin cortex from opposing cell poles and the accumulation of an actomyosin belt at the cell centre. Although these spatially distinct cortical remodelling events are coordinated in time, here we show that they are independent of each other. Thus, actomyosin is lost from opposing poles in anaphase cells that lack an actomyosin ring owing to centralspindlin depletion. In examining potential regulators of this process, we identify a role for Aurora B kinase in actin clearance at cell poles. Upon combining Aurora B inhibition with centralspindlin depletion, cells exiting mitosis fail to change shape and remain completely spherical. Additionally, we demonstrate a requirement for Aurora B in the clearance of cortical actin close to anaphase chromatin in cells exiting mitosis with a bipolar spindle and in monopolar cells forced to divide while flat. Altogether, these data suggest a novel role for Aurora B activity in facilitating DNA-mediated polar relaxation at anaphase, polarization of the actomyosin cortex, and cell division., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Clearance of mitochondria following damage is critical for neuronal homeostasis. Here, we investigate the role of Miro proteins in mitochondrial turnover by the PINK1/Parkin mitochondrial quality control system in vitro and in vivo. We find that upon mitochondrial damage, Miro is promiscuously ubiquitinated on multiple lysine residues. Genetic deletion of Miro or block of Miro1 ubiquitination and subsequent degradation lead to delayed translocation of the E3 ubiquitin ligase Parkin onto damaged mitochondria and reduced mitochondrial clearance in both fibroblasts and cultured neurons. Disrupted mitophagy in vivo, upon post-natal knockout of Miro1 in hippocampus and cortex, leads to a dramatic increase in mitofusin levels, the appearance of enlarged and hyperfused mitochondria and hyperactivation of the integrated stress response (ISR). Altogether, our results provide new insights into the central role of Miro1 in the regulation of mitochondrial homeostasis and further implicate Miro1 dysfunction in the pathogenesis of human neurodegenerative disease., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

The surge in clinical demand, shortage in personal protective equipment and high-exposure risk for healthcare workers during the COVID-19 pandemic has challenged hospital common practices and forced a reassessment of care delivery models. Code blue teams are highly specialised units that partake in life-saving situations that can jeopardise the safety of team members. There is a paucity of guidance in regards to proper infection control measures to protect the responders.This study describes a methodical approach to assessing vulnerabilities to transmission of SARS-CoV-2 within existing code blue practices, modalities to limit the number of code blue team responders and modifications to the protocol at a large community teaching hospital. The effort undertaken faced challenges due to the nature of the pandemic and the increased demand on healthcare workers. Quality improvement methods facilitated our protocol design and implementation. To this date, there has been no identified COVID-19 disease in any protected code blue (PCB) team members. We recommend that similar practices be considered and adopted widely and practised periodically., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

(1) Defining a protocol for management of patients with severe temporomandibular joint ankylosis. (2) Review the results of use of GORE-TEX as an interpositional material in gap arthroplasty. All cases which were treated with surgical intervention for severe TMJ Ankylosis with use of GORE-TEX as an interpositional material have been included. Amongst 40 patients, 11 were male and 29 were female with age group ranging from 4 to 36 years. 22 patients had bilateral ankylosis and 18 patients had unilateral ankylosis needing unilateral condylectomy. In all the patients GORE-TEX was used as an inter-positional material to form a pseudo joint. Postoperative mouth opening was around 3 fingers (3-3.5 cm) for period of 2 years i.e. last follow up. Migration or extrusion of implant was not seen in any of our cases. Use of GORE-TEX as an inter-positional material can prevent recurrences with good restoration of the physiological joint and occlusion., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2020.)

We studied the trajectories of polymers being advected while diffusing in a pressure driven flow along a periodic pillar nanostructure known as nanoscale deterministic lateral displacement (nanoDLD) array. We found that polymers follow different trajectories depending on their length, flow velocity and pillar array geometry, demonstrating that nanoDLD devices can be used as a continuous polymer fractionation tool. As a model system, we used double-stranded DNA (dsDNA) with various contour lengths and demonstrated that dsDNA in the range of 100-10 000 base pairs (bp) can be separated with a size-selective resolution of 200 bp. In contrast to spherical colloids, a polymer elongates by shear flow and the angle of polymer trajectories with respect to the mean flow direction decreases as the mean flow velocity increases. We developed a phenomenological model that explains the qualitative dependence of the polymer trajectories on the gap size and on the flow velocity. Using this model, we found the optimal separation conditions for dsDNA of different sizes and demonstrated the separation and extraction of dsDNA fragments with over 75% recovery and 3-fold concentration. Importantly, this velocity dependence provides a means of fine-tuning the separation efficiency and resolution, independent of the nanoDLD pillar geometry.

Background: In patients with colorectal cancer liver metastases (CRLM), right portal vein embolisation (RPVE) is used to increase the volume of the future remnant liver (FRL) before major hepatic resection. It is not established whether embolisation of segment 4 in addition RPVE (RPVE + 4) induces greater hypertrophy of the FRL. Limitations of prior studies include heterogenous populations and use of hypertrophy metrics sensitive to baseline variables., Methods: From 2010 to 2015, consecutive patients undergoing RPVE or RPVE + 4 for CRLM, who had not undergone prior major hepatic resection and in whom imaging was available, were included in a retrospective study. Data were extracted from hospital electronic records. Volumetric assessments of segments 2-3 were made on cross-sectional imaging before and after embolisation and corrected for standardised liver volume., Results: Ninety-nine patients underwent PVE, and 60 met the inclusion criteria. Thirty-eight patients underwent RPVE, and 22 underwent RPVE + 4. Forty-five patients had undergone median 6 cycles of prior chemotherapy. Eighteen patients had FRL metastases at PVE, and 16 had undergone subsegmental metastasectomy in the FRL. Assessments of the degree of hypertrophy (DH) of segments 2/3 were made at median 35 (interquartile range 30-49) days after PVE. RPVE + 4 resulted in a significantly greater increase in DH than RPVE (7.7 ± 1.8% vs 11.3 ± 2.6%, p = 0.011). No confounding association between baseline variables and the decision to undertake RPVE or RPVE + 4 was identified. Median survival was 2.4 years and was not influenced by segment 4 embolisation., Conclusion: RPVE + 4 results in greater DH of segments 2/3 than RPVE in people with CLRM.

Background: Endovascular intervention has emerged as a potential alternative to open surgery in treating common femoral artery (CFA) atherosclerotic disease. The aim of this systematic review was to assess the safety and efficacy of both techniques., Methods: Thirteen electronic databases from 1980 to 3 January 2018 were searched. Study quality was assessed using the National Institute for Health and Care Excellence Interventional Procedure Programme quality assessment tool. Safety and efficacy outcome measures were analysed., Results: Thirty-one studies reporting 813 endovascular procedures and 3835 endarterectomies were included. Only two small RCTs have been reported. The methodological quality of available studies was generally low and follow-up short. Safety endpoint assessment revealed a similar risk of wound haematoma for endovascular intervention and endarterectomy (5·5 (95 per cent c.i. 0·2 to 17·2) versus 3·9 (1·7 to 6·9) per cent respectively), a lower risk of wound infection with endovascular procedures (0 versus 5·9 (3·4 to 9·0) per cent) and a lower risk of wound lymph leakage (0 versus 5·7 (3·3 to 8·6) per cent). Efficacy endpoint assessment at 1 year identified that endovascular intervention had a lower primary patency rate than endarterectomy (78·8 (73·3 to 83·8) versus 96·0 (92·2 to 98·6) per cent respectively), a higher revascularization rate (16·0 (6·1 to 29·4) versus 5·8 (1·0 to 14·2) per cent) and a similar amputation rate (2·7 (1·2 to 4·8) versus 1·9 (0·7 to 3·8) per cent)., Conclusion: Endovascular intervention of CFA disease appears to reduce the risk of wound complications but is associated with a lower patency rate and increased rates of subsequent revascularization procedures. Standardization of the endovascular technique and quantification of the proportions of patients suitable for either technique are required., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Extracellular vesicles (EVs) offer many opportunities in early-stage disease diagnosis, treatment monitoring, and precision therapy owing to their high abundance in bodily fluids, accessibility from liquid biopsy, and presence of nucleic acid and protein cargo from their cell of origin. Despite their growing promise, isolation of EVs for analysis remains a labor-intensive and time-consuming challenge given their nanoscale dimensions (30-200 nm) and low buoyant density. Here, we report a simple, size-based EV separation technology that integrates 1024 nanoscale deterministic lateral displacement (nanoDLD) arrays on a single chip capable of parallel processing sample fluids at rates of up to 900 μL h-1. Benchmarking the nanoDLD chip against commonly used EV isolation technologies, including ultracentrifugation (UC), UC plus density gradient, qEV size-exclusion chromatography (Izon Science), and the exoEasy Maxi Kit (QIAGEN), we demonstrate a superior yield of ∼50% for both serum and urine samples, representing the ability to use smaller input volumes to achieve the same number of isolated EVs, and a concentration factor enhancement of up to ∼3× for both sample types, adjustable to ∼60× for urine through judicious design. Further, RNA sequencing was carried out on nanoDLD- and UC-isolated EVs from prostate cancer (PCa) patient serum samples, resulting in a higher gene expression correlation between replicates for nanoDLD-isolated EVs with enriched miRNA, decreased rRNA, and the ability to detect previously reported RNA indicators of aggressive PCa. Taken together, these results suggest nanoDLD as a promising alternative technology for fast, reproducible, and automatable EV-isolation.

Introduction: Percutaneous transluminal angioplasty (PTA), with or without stent placement, has become the treatment of choice for portal vein complications (PVC) following liver transplantation. We aimed to assess long-term outcomes of intervention in paediatric transplant recipients, in a single institution., Materials and Methods: 227 children received 255 transplants between November 2000 and September 2016. 30 patients developed PVC of whom 21 had percutaneous intervention. Retrospective clinical and procedural outcome data on these 21 patients were collected., Results: 21 patients, with median age 1.7 years (range 0.4-16.2), underwent 42 procedures with PTA with or without stenting. 36 procedures were for PV stenosis and 6 for PV thrombosis. Treatment was with primary PTA, with stenting reserved for suboptimal PTA result or restenosis within 3 months. 28 procedures were performed with PTA and 13 with stenting. Technical success (>50% reduction in mean pressure gradient, absolute pressure gradient ≤4 mmHg or venographic stenosis <30%) was achieved in 41 procedures. Failure to recanalise a thrombosed PV occurred in 1 procedure. There were no major procedural complications. Patients were followed-up with serial Doppler ultrasound surveillance. Kaplan-Meier estimated median primary patency was 9.9 months, with primary-assisted patency of 95% after median follow-up of 45.5 months (range 11.1-171.6)., Conclusion: With regular surveillance, excellent patency rates can be achieved following percutaneous intervention for PVC post-paediatric liver transplantation.

To compare the outcome of type I tympanoplasty with cortical mastoidectomy in chronic otitis media active mucosal disease (wet ear) versus chronic otitis media inactive mucosal disease (dry ear). An observational analytic study was conducted and data collection was done from August 2014 to August 2016. All patients of chronic otitis media with mucosal disease were divided into two groups, one with active disease (group A) and another with inactive disease (group B). The outcome was studied in the form of graft take up rate. Total 103 patients were studied, group A (wet ear) had 67 and group B (dry ear) had 36 patients. Graft take up rate was 94% in wet ear and 100% in dry ear and p value was 0.2. There was no statistically significant difference found between the two groups.

Background: Interleukin-10 secreting B-cells are a major subset of B-regulatory cells (B-regs), commonly recognized as CD19 + /38 hi /24 hi /IL10 + . They carry out immunomodulation by release of specific cytokines and/or cell-to-cell contact. We have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy., Material and Methods: Mononuclear cells separated by density gradient centrifugation from 50 ml anti-coagulated blood of 15-RAR and respective donors were analysed for baseline B-regs using appropriate antibodies. Equal amount (20 × 10 6  cells/ml) of stimulator (irradiated at 7.45 Gy/min for 10 min) and responder (non-irradiated) cells were co-cultured with in-vitro generated AD-MSC (1 × 10 6  cells/ml) in proliferation medium containing lipopolysaccharide from E. coli K12 strain at 37 °C with 5% CO 2 . Cells were harvested on day-7 and analyzed for viability, sterility, quantity, morphology and phenotyping. In-vitro generated B-reg levels were compared with baseline B-regs., Results: In-vitro generated B-reg count increased to 16.75% from baseline count of 3.35%., Conclusion: B-regs can be successfully generated in-vitro from donor AD-MSC and RAR PBMC for potential cell therapy., (Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Wafer-scale fabrication of complex nanofluidic systems with integrated electronics is essential to realizing ubiquitous, compact, reliable, high-sensitivity and low-cost biomolecular sensors. Here we report a scalable fabrication strategy capable of producing nanofluidic chips with complex designs and down to single-digit nanometre dimensions over 200 mm wafer scale. Compatible with semiconductor industry standard complementary metal-oxide semiconductor logic circuit fabrication processes, this strategy extracts a patterned sacrificial silicon layer through hundreds of millions of nanoscale vent holes on each chip by gas-phase Xenon difluoride etching. Using single-molecule fluorescence imaging, we demonstrate these sacrificial nanofluidic chips can function to controllably and completely stretch lambda DNA in a two-dimensional nanofluidic network comprising channels and pillars. The flexible nanofluidic structure design, wafer-scale fabrication, single-digit nanometre channels, reliable fluidic sealing and low thermal budget make our strategy a potentially universal approach to integrating functional planar nanofluidic systems with logic circuits for lab-on-a-chip applications.

A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions. MSC have the capacity to tweak endogenous tissue and cells of immune system. They have been proven as secure and efficacious cell-based regenerative therapy, to treat diverse autoimmune, degenerative diseases and tissue injuries. By consolidating characteristics of MSC biology, MSC-based therapy, engineering and advances in the field, MSC have a great potential to bring us notably closer to a much-needed and long-time awaited cure of IDDM. The review discusses MSC-based cellular therapeutic strategies targeting at IDDM. MSC characteristics of immunomodulation and regeneration potential when used alone or in combination with islets or in differentiated form of insulin producing cells (IPC) are taken into consideration for the review purpose., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Introduction: Post-EVAR surveillance has a major impact upon patients, carers and healthcare resources. We hypothesised that elective indication, on-IFU anatomy, use of a modern device or normal first CTA, or a combination of these categories, might predict a rate of secondary intervention low enough to alter current surveillance protocols., Methods: Patients undergoing EVAR in our institution between 01.05.2007 and 28.02.2013 were assessed. Data on indication (elective, emergency), anatomy relative to IFU, device, first month CTA result, secondary intervention and mortality were obtained. Kaplan-Meier charts of mortality and freedom from secondary intervention were produced. Statistical analysis was by log-rank test and Cox proportional hazard modelling., Results: 234 patients underwent EVAR (188 elective, 208 on-IFU). Most implants were Endurant (106) or Talent (98). 151 patients had a normal first CTA. By median follow-up of 38.6 months, 39 patients underwent secondary intervention. A normal first CTA and elective indication were significantly associated with reduced risk of secondary intervention (p < 0.001 and p = 0.042 respectively), but device type and placement on- or off-IFU were not. Elective placement with a normal first CTA was 93 % predictive of freedom from secondary intervention by 32 months post-EVAR. Of nine patients undergoing secondary intervention in this group, eight presented symptomatically., Discussion: In optimal procedural circumstances with normal post-procedural imaging, only 7 % of patients undergoing EVAR require secondary intervention, a minority of which is driven by surveillance. These data support a change to surveillance more tailored to the individual patient, and highlight the need for further qualitative and quantitative research.

Aim: To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives., Methods: A systematic literature search was performed using electronic literature databases using various search terms. The International Diabetes Federation World Atlas was used to generate a list of populations with high rates of diabetes. PubMed, Scopus and Google Scholar were used to identify which of these populations also had a reported prevalence of haemoglobin abnormalities., Results: Abnormalities in iron homeostasis leads to increases in reactive oxygen species in the blood. This promotes oxidative stress which contributes to peripheral resistance to insulin in two ways: (1) reduced insulin/insulin receptor interaction; and (2) β-cell dysfunction. Hepcidin is crucial in terms of maintaining appropriate amounts of iron in the body and is in turn affected by haemoglobinopathies. Hepcidin also has other metabolic effects in places such as the liver but so far the extent of these is not well understood. It does however directly control the levels of serum ferritin. High serum ferritin is found in obese patients and those with diabetes and a meta-analysis of the various studies shows that high serum ferritin does indeed increase diabetes risk., Conclusion: From an epidemiological standpoint, it is plausible that the well-documented protective effects of haemoglobinopathies with regard to malaria may have also offered other evolutionary advantages. By contributing to peripheral insulin resistance, haemoglobinopathies may have helped to sculpt the so-called "thrifty genotype", which hypothetically is advantageous in times of famine. The prevalence data however is not extensive enough to provide concrete associations between diabetes and haemoglobinopathies - more precise studies are required.