A stroke/vascular neurology service increases the volume of urgent carotid endarterectomies performed in a tertiary referral center.

BACKGROUND: Increasing evidence supports that urgent carotid endarterectomy (CEA), defined as CEA during the index hospitalization, may be undertaken in select patients with acute carotid-related neurologic symptoms to prevent recurrent ischemic events. We aimed to determine the effect of a stroke/vascular neurology service on the volume of urgent CEAs performed and assess perioperative outcomes. METHODS: A retrospective review from a single tertiary referral center between June 2005 through December 2011 revealed 393 patients who underwent CEA. We identified the number of urgent CEAs before (June 2005-August 2008) and after (September 2008-December 2011) a stroke/vascular neurology service was implemented, as well as asymptomatic CEAs and symptomatic but electively performed CEAs. Demographic data as well as 30-day adverse outcomes (transient ischemic attack [TIA], stroke, myocardial infarction, and mortality) were analyzed for each group. In patients undergoing urgent CEA, TIA and stroke severity were assessed by a stroke neurologist using the ABCD2 TIA score and National Institutes of Health Stroke Scale (NIHSS), respectively. The χ2 test was used to compare differences between the urgent CEA volume before and after a stroke/vascular neurology service. Fisher's exact test was used to analyze perioperative outcomes. RESULTS: Demographics and comorbidities were similar between the 2 groups. The proportion of urgent CEAs performed increased significantly after initiation of a vascular neurology service (4.1% [7 of 172] vs. 22.2% [49 of 221], P<0.0001). Per annum, urgent CEAs increased from 5.3% (4/75) in 2005 to 39.6% (25/63) in 2011. A vascular neurology service did not increase the number of nonurgent referrals. Urgent CEA indications were ocular ischemic events 4% (2/49), cerebral ischemic/infarction events 35% (17/49), crescendo TIAs 6% (3/49), acute stroke 45% (22/49), and stroke-in-evolution 10% (5/49). Mean NIHSS was 3.5 (range 0-24); mean TIA score was 5 (range 1-8). Although there were no statistical differences in 30-day outcomes, there was a trend toward a higher combined complication rate (stroke, death, myocardial infarction) in the urgent compared with the symptomatic but electively performed CEA group (7.1 % [3/49] vs. 2% [1/49]; P=.36). However, patients undergoing urgent CEA with an NIHSS<10 had no perioperative complications. CONCLUSIONS: Collaboration with a vascular neurology team increased the volume of urgent CEAs over a 3-year period. In patients with mild-to-moderate strokes (NIHSS<10), urgent CEA perioperative outcomes approximate those for electively performed CEAs, suggesting improved care through a multidisciplinary approach.

A technique for a bloodless tracheostomy in an anticoagulated patient on extracorporeal membrane oxygenation.

A tracheostomy is a commonly indicated procedure for ventilated patients with respiratory failure expected to have a prolonged ventilator wean. In patients who are fully anticoagulated and on extracorporeal membrane oxygenation, it is our practice to perform a tracheostomy with a surgical technique rather than to ensure haemostasis percutaneously. A surgical tracheostomy is a safe procedure for patients on extracorporeal membrane oxygenation, provided it is being done in an experienced centre. If the risk of interrupting anticoagulation permits, we stop the unfractionated heparin infusion 4 hours prior to the procedure. This video tutorial describes the principles of a surgical tracheostomy, our bloodless technique and the relevant anatomy and equipment.

Attitudes and beliefs of South African medical students toward organ transplantation.

The aim of this study was to assess and analyse the attitudes and beliefs of medical students regarding organ donation, procurement, and transplantation. Medical students at the University of Cape Town were prospectively surveyed using a self-administered questionnaire. There were 346 study participants; the mean age was 21 (range 18-33) yr, 38% were male and 62% was female. Only 8% of respondents were registered donors; clinical and white students constituted the majority of this group. Of the 315 "non-donors," the main reason for not donating was "I have not really thought about organ donation" (59%). Most students (91%) would accept an artificial organ; and 87% and 52% of students would accept human and animal organs respectively. Muslim students (11%, p<0.05) and those who believe in an after-life or reincarnation (18%, p=0.00) were less willing to accept human or animal organs. About 95% of respondents stated that they would like to learn more about transplantation and would keep information about it in their practice but only 18% of respondents knew where to find information for potential donors and recipients. Most students have a favorable attitude toward organ transplantation; religion and belief systems impact on willingness to receive organs.

How to optimize your set-up for a VATS right upper lobectomy.

A 77-year-old woman with multiple ground-glass opacities, the largest of which measured 21 mm, has a biopsy-proven primary lung adenocarcinoma in her right upper lobe. We performed a 3-port right-sided VATS using the Copenhagen approach. There was no pleural effusion or evidence of pleural metastatic spread. A tumor was identified in the upper lobe. The surrounding lung tissue appeared normal.  We performed a multilevel intercostal block using 0.25% levobupivacaine. The inferior pulmonary ligament was divided. The superior pulmonary vein and 2 branches of the pulmonary artery to the right upper lobe were dissected, encircled, and divided using tan reloads of the Endo GIA stapler. The right upper lobe bronchus was dissected, encircled, and divided in a similar fashion using a purple reload of the Endo GIA stapler following a successful test inflation of the lower and middle lobes. The horizontal fissure was completed with further firings of the stapler. Lymph nodes from stations 2, 4, 7, 8, 9, 10, and 11 were sampled and sent separately for histological analysis. There was no parenchymal or stump leak to 20 cm H20 on the test inflation. Hemostasis and pneumostasis were checked and ensured. A single 24 Fr drain was placed in the apex. Hemostasis was complete. The incision was closed in layers.

Maintaining safe lung cancer surgery during the COVID-19 pandemic in a global city.

BACKGROUND: SARS-CoV-2 has challenged health service provision worldwide. This work evaluates safe surgical pathways and standard operating procedures implemented in the high volume, global city of London during the first wave of SARS-CoV-2 infection. We also assess the safety of minimally invasive surgery(MIS) for anatomical lung resection. METHODS: This multicentre cohort study was conducted across all London thoracic surgical units, covering a catchment area of approximately 14.8 Million. A Pan-London Collaborative was created for data sharing and dissemination of protocols. All patients undergoing anatomical lung resection 1st March-1st June 2020 were included. Primary outcomes were SARS-CoV-2 infection, access to minimally invasive surgery, post-operative complication, length of intensive care and hospital stay (LOS), and death during follow up. FINDINGS: 352 patients underwent anatomical lung resection with a median age of 69 (IQR: 35-86) years. Self-isolation and pre-operative screening were implemented following the UK national lockdown. Pre-operative SARS-CoV-2 swabs were performed in 63.1% and CT imaging in 54.8%. 61.7% of cases were performed minimally invasively (MIS), compared to 59.9% pre pandemic. Median LOS was 6 days with a 30-day survival of 98.3% (comparable to a median LOS of 6 days and 30-day survival of 98.4% pre-pandemic). Significant complications developed in 7.3% of patients (Clavien-Dindo Grade 3-4) and 12 there were re-admissions(3.4%). Seven patients(2.0%) were diagnosed with SARS-CoV-2 infection, two of whom died (28.5%). INTERPRETATION: SARS-CoV-2 infection significantly increases morbidity and mortality in patients undergoing elective anatomical pulmonary resection. However, surgery can be safely undertaken via open and MIS approaches at the peak of a viral pandemic if precautionary measures are implemented. High volume surgery should continue during further viral peaks to minimise health service burden and potential harm to cancer patients. FUNDING: This work did not receive funding.

Impact of a streamlined rotational system for the management of acute aortic syndrome: sharing is caring†.

OBJECTIVES: Acute type A aortic dissection is an emergency associated with up to 30% of hospital mortality. It has been established that outcomes are improved with specialist aortic team care in high-volume centres. Most centres are limited to a small number of aortic specialists, thus making it logistically impractical to have a dedicated 24/7 single-centre service. In 2011, a rotational 24/7 service between 3 centres covering a geographical location was introduced including 24/7 access to a dissection 'Hotline'. METHODS: We analysed data since 2003 from a prospectively collected database. A total of 227 patients underwent surgery for acute aortic syndrome between 2003 and 2017. The results on outcomes were compared before and after the initiation of the dissection hotline and 24/7 dedicated service. RESULTS: We identified 128 patients from the pre-rotational group and 99 patients from the post-rotational group. Both groups were well matched in terms of demographics and comorbidities. In the post-rotational group, there was an increase in arch surgery (11.8% vs 20.2%, P: 0.07). The introduction of the rotational service reduced 30-day mortality (20% vs 8%, P: 0.010). The introduction of the service improved the overall long-term survival [P: 0.04, hazard ratio 1.86; confidence interval (1.03-3.38)] in the multivariable analysis. There was no difference between the groups in postoperative complications. There was an increase in the median length of hospital stay in the post-rotational group (13 days vs 20 days, P: 0.014). CONCLUSIONS: A streamlined aortic dissection service allows for centralized care. This provides the referring centres with 24/7 access to an experienced aortic team and may improve patient outcomes.

The Ensemble Mars Atmosphere Reanalysis System (EMARS) Version 1.0.

The Ensemble Mars Atmosphere Reanalysis System (EMARS) dataset version 1.0 contains hourly gridded atmospheric variables for the planet Mars, spanning Mars Year (MY) 24 through 33 (1999 through 2017). A reanalysis represents the best estimate of the state of the atmosphere by combining observations that are sparse in space and time with a dynamical model and weighting them by their uncertainties. EMARS uses the Local Ensemble Transform Kalman Filter (LETKF) for data assimilation with the GFDL/NASA Mars Global Climate Model (MGCM). Observations that are assimilated include the Thermal Emission Spectrometer (TES) and Mars Climate Sounder (MCS) temperature retrievals. The dataset includes gridded fields of temperature, wind, surface pressure, as well as dust, water ice, CO2 surface ice and other atmospheric quantities. Reanalyses are useful for both science and engineering studies, including investigations of transient eddies, the polar vortex, thermal tides and dust storms, and during spacecraft operations.

Evaluating and Extending the Ocean Wind Climate Data Record.

Satellite microwave sensors, both active scatterometers and passive radiometers, have been systematically measuring near-surface ocean winds for nearly 40 years, establishing an important legacy in studying and monitoring weather and climate variability. As an aid to such activities, the various wind datasets are being intercalibrated and merged into consistent climate data records (CDRs). The ocean wind CDRs (OW-CDRs) are evaluated by comparisons with ocean buoys and intercomparisons among the different satellite sensors and among the different data providers. Extending the OW-CDR into the future requires exploiting all available datasets, such as OSCAT-2 scheduled to launch in July 2016. Three planned methods of calibrating the OSCAT-2 σo measurements include 1) direct Ku-band σo intercalibration to QuikSCAT and RapidScat; 2) multisensor wind speed intercalibration; and 3) calibration to stable rainforest targets. Unfortunately, RapidScat failed in August 2016 and cannot be used to directly calibrate OSCAT-2. A particular future continuity concern is the absence of scheduled new or continuation radiometer missions capable of measuring wind speed. Specialized model assimilations provide 30-year long high temporal/spatial resolution wind vector grids that composite the satellite wind information from OW-CDRs of multiple satellites viewing the Earth at different local times.

Domain organization of D-AKAP2 revealed by enhanced deuterium exchange-mass spectrometry (DXMS).

Dual specific A-kinase anchoring protein 2 (D-AKAP2) is a scaffold protein that coordinates cAMP-mediated signaling complexes by binding to type I and type II protein kinase A (PKA). While information is unfolding regarding specific binding motifs, very little is known about the overall structure and dynamics of these scaffold proteins. We have used deuterium exchange-mass spectrometry (DXMS) and limited proteolysis to probe the folded regions of D-AKAP2, providing for the first time insight into the intra-domain dynamics of a scaffold protein. Deuterium on-exchange revealed two regions of low deuterium exchange that were surrounded by regions of high exchange, suggestive of two distinctly folded regions, flanked by disordered or solvent accessible regions. Similar folded regions were detected by limited proteolysis. The first folded region contained a putative regulator of G-protein signaling (RGS) domain. A structural model of the RGS domain revealed that the more deuterated regions mapped onto loops and turns, whereas less deuterated regions mapped onto alpha-helices, consistent with this region folding into an RGS domain. The second folded region contained a highly protected PKA binding site and a more solvent-accessible PDZ binding motif, which may serve as a potential targeting domain for D-AKAP2. DXMS has verified the multi-domain architecture of D-AKAP2 implied by sequence homology and has provided unique insight into the accessibility of the PKA binding site.

Thrittene, homologous with somatostatin-28((1-13)), is a novel peptide in mammalian gut and circulation.

Preprosomatostatin is a gene expressed ubiquitously among vertebrates, and at least two duplications of this gene have occurred during evolution. Somatostatin-28 (S-28) and somatostatin-14 (S-14), C-terminal products of prosomatostatin (ProS), are differentially expressed in mammalian neurons, D cells, and enterocytes. One pathway for the generation of S-14 entails the excision of Arg13-Lys14 in S-28, leading to equivalent amounts of S-28((1-12)). Using an antiserum (F-4), directed to the N-terminal region of S-28 that does not react with S-28((1-12)), we detected a peptide, in addition to S-28 and ProS, that was present in human plasma and in the intestinal tract of rats and monkeys. This F-4 reacting peptide was purified from monkey ileum; and its amino acid sequence, molecular mass, and chromatographic characteristics conformed to those of S-28((1-13)), a peptide not described heretofore. When extracts of the small intestine were measured by RIA, there was a discordance in the ratio of peptides reacting with F-4 and those containing the C terminus of ProS, suggesting sites of synthesis for S-28((1-13)) distinct from those for S-14 and S-28. This was supported by immunocytochemistry, wherein F-4 reactivity was localized in gastrointestinal (GI) endocrine cells and a widespread plexus of neurons within the wall of the distal gut while immunoreactivity to C-terminal domains of S-14 and S-28 in these neurons was absent. Further, F-4 immunoreactivity persisted in similar GI endocrine cells and myenteric neurons in mice with a targeted deletion of the preprosomatostatin gene. We believe that these data suggest a novel peptide produced in the mammalian gut, homologous with the 13 residues of the proximal region of S-28 but not derived from the ProS gene. Pending characterization of the gene from which this peptide is derived, its distribution, and function, we have designated this peptide as thrittene. Its localization in both GI endocrine cells and gut neurons suggests that thrittene may function as both a hormone and neurotransmitter.

The UCT Surgical Society - a society on the cutting edge.

The University of Cape Town Surgical Society is a student-run society established in 2006 and is affiliated with the Department of Surgery. The aims of the society are to supplement undergraduate training, to promote medical and surgical research, and to motivate students to pursue a career in surgery. Regular monthly lectures and surgical skills courses are offered, as well as weekly anatomy workshops. A recently launched Shadow Programme enables students to interact with practising surgeons in theatre, thereby gaining insight into the advantages and challenges involved in a future career in surgery.

Structural characterization of recombinant soluble rat neuroligin 1: mapping of secondary structure and glycosylation by mass spectrometry.

Neuroligins (NLs) are a family of transmembrane proteins that function in synapse formation and/or remodeling by interacting with beta-neurexins (beta-NXs) to form heterophilic cell adhesions. The large N-terminal extracellular domain of NLs, required for beta-NX interactions, has sequence homology to the alpha/beta hydrolase fold superfamily of proteins. By peptide mapping and mass spectrometric analysis of a soluble recombinant form of NL1, several structural features of the extracellular domain have been established. Of the nine cysteine residues in NL1, eight are shown to form intramolecular disulfide bonds. Disulfide pairings of Cys 117 to Cys 153 and Cys 342 to Cys 353 are consistent with disulfide linkages that are conserved among the family of alpha/beta hydrolase proteins. The disulfide bond between Cys 172 and Cys 181 occurs within a region of the protein encoded by an alternatively spliced exon. The disulfide pairing of Cys 512 and Cys 546 in NL1 yields a structural motif unique to the NLs, since these residues are highly conserved. The potential N-glycosylation sequons in NL1 at Asn 109, Asn 303, Asn 343, and Asn 547 are shown occupied by carbohydrate. An additional consensus sequence for N-glycosylation at Asn 662 is likely occupied. Analysis of N-linked oligosaccharide content by mass matching paradigms reveals significant microheterogeneous populations of complex glycosyl moieties. In addition, O-linked glycosylation is observed in the predicted stalk region of NL1, prior to the transmembrane spanning domain. From predictions based on sequence homology of NL1 to acetylcholinesterase and the molecular features of NL1 established from mass spectrometric analysis, a novel topology model for NL three-dimensional structure has been constructed.

Purification and identification of protein-tyrosine kinase-binding proteins using synthetic phosphopeptides as affinity reagents.

Protein-tyrosine kinases are known regulators of cell division that have been implicated in the onset of a variety of malignancies. They act through cellular signaling proteins that bind to specific autophosphorylation sites. To find out whether these autophosphorylation sites can be used to identify downstream signaling proteins, synthetic peptides based on an autophosphorylation site in the colony-stimulating factor-1 (CSF-1) receptor were linked to agarose beads and incubated with lysates from macrophages. Bound proteins were analyzed by MS, leading to the identification of both known and novel CSF-1 receptor-interacting proteins. The approach presented here can be applied to phosphorylation sites in a wide variety of proteins. It will lead to the identification of novel protein-protein interactions and provide new insights into the mechanics of signal transduction. Novel protein-protein interactions may provide useful targets for the development of drugs that interfere with the activation of signaling cascades used by protein-tyrosine kinases to turn on cell division.