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"Kirk, Alan"
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A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM)
by
Garner, Justin L.
,
Slebos, Dirk-Jan
,
Trosini-Desert, Valéry
in
Chronic obstructive pulmonary disease
,
Clinical trials
,
collateral ventilation
2017
Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach.
To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation.
This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV
improvement from baseline of 12% or greater. Changes in FEV
, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months.
Ninety seven subjects were randomized to EBV (n = 65) or SoC (n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV
improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean ± SD change in FEV
at 6 months of 20.7 ± 29.6% and -8.6 ± 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 ± 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: ΔEBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George's Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, -1.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects.
EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT02022683).
Journal Article
Exploration for olive fruit fly parasitoids across Africa reveals regional distributions and dominance of closely associated parasitoids
by
Walton, Vaughn M.
,
Pickett, Charles H.
,
Straser, Robert K.
in
631/158/2178
,
631/158/2458
,
Adaptation
2021
The olive fruit fly,
Bactrocera oleae
, has been a key pest of olives in Europe and North America. We conducted the largest exploration for parasitoids associated with the fly across Sub-Saharan Africa (Kenya, Namibia, and South Africa) including some of the fly’s adjoining regions (Canary Islands, Morocco, Réunion Island and Tunisia). From Sub-Saharan regions, four braconids were collected:
Bracon celer
,
Psytallia humilis, P. lounsburyi
, and
Utetes africanus
. Results showed that their regional dominance was related to climate niches, with
P. humilis
dominant in hot semi-arid areas of Namibia,
P. lounsburyi
dominant in more tropical areas of Kenya, and
U. africanus
prevalent in Mediterranean climates of South Africa.
Psytallia concolor
was found in the Canary Islands, Morocco and Tunisian, and the Afrotropical braconid
Diachasmimorpha
sp. near
fullawayi
on Réunion Island. Furthermore, we monitored the seasonal dynamics of the fly and parasitoids in Cape Province of South Africa. Results showed that fruit maturity, seasonal variations in climates and interspecific interactions shape the local parasitoid diversity that contribute to the low fly populations. The results are discussed with regard to ecological adaptations of closely associated parasitoids, and how their adaptations impact biocontrol.
Journal Article
A case series of pulmonary resection for metastatic colorectal cancer in a UK regional thoracic center
2015
Pulmonary metastasectomy has become an established mode of therapy in the management of certain patients with metastatic colorectal cancer. All patients undergoing pulmonary resection for metastatic colorectal cancer between March 2008 and February 2014 were studied. 190 patients were identified. Most had a single metastasis (83%); 17% had multiple lesions (maximum: 4). The approach was thoracotomy in 92 and VATS in 98. 67% underwent wedge resection and 33% lobectomy. The size of the resected lesions was 8-110 mm (median: 24). 13% of patients underwent more than one procedure (maximum: 4); 8% had prior hepatic metastasectomy. There was no operative mortality. The 1-, 3- and 5-year survival was 92, 87 and 82%, respectively. Guidelines for referral and follow-up of these patients should be developed.
Journal Article
Detection of a Diverse Endophyte Assemblage within Fungal Communities Associated with the Arundo Leaf Miner, Lasioptera donacis (Diptera: Cecidomyiidae)
2023
The larvae of Lasioptera donacis Coutin feed on fungal communities lining galleries within the mesophyll of leaf sheaths of Arundo donax in an aggregative manner. It has been stated that L. donacis could have established a fundamental symbiotic relationship with one fungus, although the fungal composition of these communities remains unsettled. Using a culture-dependent approach and ITS sequencing, the present work characterizes and compares the fungal communities associated with L. donacis in Eurasia with the endophytes of A. donax in Texas where L. donacis is absent. The 65 cultivable isolates obtained from L. donacis fungal communities were sorted into 15 MOTUs, among which Fusarium and Sarocladium predominated. No particular MOTU was systematically recovered from these communities regardless of the sites. The 19 isolates obtained in Texas were sorted into 11 MOTUs. Sarocladium and Fusarium were commonly found in Texas and Eurasia. Our finding indicate that the communities were composed of a diverse assemblage of non-systemic endophytes, rather than an exclusive fungal symbiont. From ovipositors and ovarioles of L. donacis emerging from plants in France, we opportunistically isolated the endophyte Apiospora arundinis, which lies at the origin of further research pertaining to its role in the feeding and oviposition of L. donacis.
Journal Article
Multidisciplinary paper on patient blood management in cardiothoracic surgery in the UK: perspectives on practice during COVID-19
by
Loubani, Mahmoud
,
Meybohm, Patrick
,
Al-Attar, Nawwar
in
Best practice
,
Bleeding
,
Blood management
2023
The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK.
Journal Article
Endothelial glycocalyx layer shedding following lung resection
by
Arthur, Alexander
,
McCall, Phillip J
,
Jolly, Lisa
in
acute lung injury
,
Acute Lung Injury - pathology
,
Aged
2016
We investigated if the serum biomarkers of endothelial glycocalyx layer (EGL) disruption, heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC1) were elevated following lung resection surgery.
Plasma samples were collected from 16 patients undergoing lobectomy for primary lung cancer. HSPG and SDC1 were measured at five perioperative timepoints. Postoperative oxygenation was recorded.
pair wise comparisons showed SDC1 concentration was significantly elevated on postoperative day 2, p < 0.001. There was no relationship found between HSPG or SDC1 levels and postoperative oxygenation.
Our pilot study is the first to provide evidence of EGL disruption following lung resection surgery. We hypothesize that EGL disruption is involved in the pathogenesis of post-lung resection acute lung injury.
This work was presented in a part at the Anaesthetic Research Society Spring Meeting, Royal College of Anaesthetists, London, UK, 22 April 2015.
Journal Article
Microsatellites Uncover Multiple Introductions of Clonal Giant Reed (Arundo donax)
2013
Giant reed (Arundo donax) is an invasive weed that is native to the Old World. Tens of thousands of hectares of riparian habitat in the Rio Grande Basin (RGB) in Texas and Mexico have been heavily affected by invasions of Arundo. Additionally, many other watersheds across the southwestern United States have also been affected. Giant reed is being targeted for biological control because it displaces native vegetation and consumes water that could potentially be used for agricultural and municipal purposes, especially in areas with limited access to water. Finding the best-adapted insects for biological control involves locating the origin(s) of this plant. To narrow down the proximal source(s) of invasion of giant reed in the RGB, 10 microsatellite markers were developed. An analysis of 203 Old World and 159 North American plants, with an emphasis on the RGB, indicated a reduction in the allelic diversity in the introduced range compared with the Old World. Clonal assignment, neighbor joining, principal coordinates analyses, and STRUCTURE analyses were consistent and implied multiple introductions in North America, with one (likely clonal) lineage responsible for the invasion of the RGB, northern Mexico, and other parts of the southwestern United States. Although no identical matches with the RGB lineage were found in the Old World, several close matches were found on the Mediterranean coast of Spain. Nomenclature: Giant reed, Arundo donax L Management Implications: Giant reed is a clonal, rhizomatous grass that has invaded tens of thousands of hectares of riparian habitat throughout the Rio Grande Basin (RGB) and other parts of the southwestern United States. In this paper, we used microsatellites to determine the original population source(s) of the invasive Arundo donax in the RGB to locate biocontrol agents from the Old World. Biological control is deemed the best long-term option for control of giant reed. Chemical and mechanical control of A. donax is expensive, especially in heavily affected areas. Although A. donax is clonal, some genetic variation was found throughout the RGB. We also discovered multiple introductions in the United States, but only one lineage is responsible for the invasion in the RGB. This indicates that a limited sampling of biocontrol insects might be effective in controlling A. donax along the Rio Grande. Additionally, these biocontrol agents might also be effective in controlling giant reed in others areas where this lineage has been introduced, such as California and Mexico.
Journal Article
MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial
by
Freeman, Carol
,
Waller, David A
,
Brown, Louise
in
Adult
,
asbestos induced lung disease
,
Cancer therapies
2019
IntroductionOne of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.Methods and analysisMesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.Ethics and disseminationThis study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.Trial registration NCT03412357.
Journal Article
132 Thymectomy for myasthenia gravis in the West of Scotland: a retrospective study
2022
The international thymectomy trial (MGTX) demonstrated benefits in myasthenia gravis (MG) patients without thymoma and up to the age of 65 years. This data and the increased availability of minimally invasive thymectomy surgery has resulted in an increasing number of patients being referred for thymec- tomy. We evaluated the clinical outcomes after thymectomy in 61 MG patients with or without thymic epithelial tumours (TET) from the West of Scotland Myasthenia database over a 10-year period.All patients had positive acetylcholine receptor antibodies. Twenty-five (41%) patients were male. Fifty-five (90.2%) had generalised MG (27 patients with TET [TET-MG], all thymoma except for one with squamous cell thymic carcinoma; 28 patients without TET [non-TET-MG]) and 6 (9.8%) had ocular MG (including 3 TET-MG patients with thymoma). Overall, age at onset and diagnosis were comparable, with a lower median age at onset for female MG patients without TET. More severe symptoms at onset and at nadir were noted in TET-MG patients.MGFA-post intervention status was similar in both groups, although more MG relapses were observed in the TET-MG group. TET-MG patients had slightly worse disease severity and outcomes. However, the two groups were largely comparable in their MG status and the therapies they received.vallyfenech@gmail.com91
Journal Article
Pancreatic Islet Transplantation Using the Nonhuman Primate (Rhesus) Model Predicts That the Portal Vein Is Superior to the Celiac Artery as the Islet Infusion Site
by
David M. Harlan
,
Janet Lee
,
Noelle Patterson
in
Animals
,
Arginine - pharmacology
,
Biological and medical sciences
2002
Pancreatic Islet Transplantation Using the Nonhuman Primate (Rhesus) Model Predicts That the Portal Vein Is Superior to the
Celiac Artery as the Islet Infusion Site
Boaz Hirshberg 1 ,
Sean Montgomery 1 ,
Michael G. Wysoki 2 ,
He Xu 1 ,
Doug Tadaki 1 ,
Janet Lee 3 ,
Kenneth Hines 3 ,
Jason Gaglia 1 ,
Noelle Patterson 1 ,
John Leconte 1 ,
Douglas Hale 1 ,
Richard Chang 4 ,
Alan D. Kirk 1 and
David M. Harlan 1
1 National Institute of Diabetes and Digestive and Kidney Diseases/Navy Transplantation & Autoimmunity Branch, Bethesda, Maryland
2 Radiology Department, Yale University, New Haven, Connecticut
3 Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
4 Radiology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
Abstract
We’ve established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets
into the gut’s arterial system would more safely and as effectively support long-term islet allograft survival compared with
the traditional portal vein approach. We reasoned that islets make up <2% of pancreatic cell mass but consume an estimated
20% of arterial blood flow, suggesting an advantage for the arterial site. Access to the arterial system is also easier and
safer than the portal system. Pancreatectomized rhesus macaques were transplanted with allogeneic islets infused into either
the portal vein ( n = 6) or the celiac artery ( n = 4). To prevent rejection, primates were given daclizumab, tacrolimus, and rapamycin. In five of six portal vein experiments,
animals achieved normoglycemia without exogenous insulin. In contrast, none of the animals given intra-arterial islets showed
even transient insulin independence ( P = 0.048). Two of the latter animals received a second islet transplant, this time to the portal system, and both achieved
insulin independence. Thus, intraportal islet transplantation under conventional immunosuppression is feasible in primates
and can result in long-term insulin independence when adequate immunosuppression is maintained. Arterial islet injection,
however, does not appear to be a viable islet transplantation technique.
Footnotes
Address correspondence and reprint requests to Dr. Boaz Hirshberg, National Institute of Diabetes and Digestive and Kidney
Diseases/Navy Transplantation & Autoimmunity Branch, 10 Center Dr., Bldg. 10, Rm. 11S219, Bethesda, MD 20889. E-mail: boazh{at}intra.niddk.nih.gov .
Received for publication 13 September 2001 and accepted in revised form 3 April 2002.
IEQ, islet equivalent; MHC, major histocompatibility complex; NIH, National Institutes of Health.
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Journal Article