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Quantum circuits interact with the environment via several temperature-dependent degrees of freedom. Multiple experiments to-date have shown that most properties of superconducting devices appear to plateau out at T ≈ 50 mK - far above the refrigerator base temperature. This is for example reflected in the thermal state population of qubits, in excess numbers of quasiparticles, and polarisation of surface spins - factors contributing to reduced coherence. We demonstrate how to remove this thermal constraint by operating a circuit immersed in liquid 3He. This allows to efficiently cool the decohering environment of a superconducting resonator, and we see a continuous change in measured physical quantities down to previously unexplored sub-mK temperatures. The 3He acts as a heat sink which increases the energy relaxation rate of the quantum bath coupled to the circuit a thousand times, yet the suppressed bath does not introduce additional circuit losses or noise. Such quantum bath suppression can reduce decoherence in quantum circuits and opens a route for both thermal and coherence management in quantum processors.
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The nature of the antiferromagnetic order in the heavy fermion metal YbRh_{2}Si_{2}, its quantum criticality, and superconductivity, which appears at low mK temperatures, remain open questions. We report measurements of the heat capacity over the wide temperature range 180 µK-80 mK, using current sensing noise thermometry. In zero magnetic field we observe a remarkably sharp heat capacity anomaly at 1.5 mK, which we identify as an electronuclear transition into a state with spatially modulated electronic magnetic order of maximum amplitude 0.1 µ_{B}. We also report results of measurements in magnetic fields in the range 0 to 70 mT, applied perpendicular to the c axis, which show eventual suppression of this order. These results demonstrate a coexistence of a large moment antiferromagnet with putative superconductivity.
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Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual's interaction with its environment. We tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including social associations, to immune phenotypes. We found that the more associated two individuals were, the more similar their immune phenotypes were. Social association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or worm infection status. These results highlight the importance of social networks for immune phenotype and reveal important immunological correlates of social life.
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Because of the extreme purity, lack of disorder, and complex order parameter, the first-order superfluid 3He A-B transition is the leading model system for first order transitions in the early universe. Here we report on the path dependence of the supercooling of the A phase over a wide range of pressures below 29.3 bar at nearly zero magnetic field. The A phase can be cooled significantly below the thermodynamic A-B transition temperature. While the extent of supercooling is highly reproducible, it depends strongly upon the cooling trajectory: The metastability of the A phase is enhanced by transiting through regions where the A phase is more stable. We provide evidence that some of the additional supercooling is due to the elimination of B phase nucleation precursors formed upon passage through the superfluid transition. A greater understanding of the physics is essential before 3He can be exploited to model transitions in the early universe.
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INTRODUCTION: Clinical visits (work experience opportunities) are a recommended part of admissions processes for many diagnostic and therapeutic radiography courses but not for operating department practice (ODP) where observational visits are challenging for applicants to obtain. The Covid-19 pandemic interrupted access to visits for all prospective students; this study presents a review of the value of clinical visits and alternatives. METHODS: This article reports the initial qualitative phase of a three-phase mixed methods study. Using a critical realist approach, focus groups explored first year student experiences of the 'ideal' pre-admission clinical visit and alternative resources. A structured review of Online Prospectus (OLP) entries was undertaken by two student researchers to ascertain the requirements for clinical visits for the three professions. RESULTS: Four focus groups included 25 first year students interviewed prior to their first clinical placement (14 therapeutic radiography, 5 diagnostic radiography and 6 ODP students). Three themes were constructed, namely: informing career choices, the clinical visit experience, and the value of clinical visits. Clinical visits affirmed rather than inspired career choices. The best timing for a visit was before admission interviews and optimal duration was a full day. Interacting with current students was the most valued aspect. Videos and simulations provided in-depth information about the professional role and allowed replay, but some participants found the videos uninspiring. OLP entries present a confusing picture for applicants who may be researching several Universities and professions. CONCLUSION: Clinical visits were deemed 'vital' to radiography student career choices, yet ODPs who could not access visits were comfortable with videos. Simulated visits are a safe option amidst the pandemic but must capture the dynamic and patient-centred nature of practice to accurately inform career choices.
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COVID-19 , Pandemias , Teste para COVID-19 , Escolha da Profissão , Humanos , Radiografia , EstudantesRESUMO
Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx), which in turn accelerate pulmonary function decline and decrease survival rate. An overarching challenge is that there is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant research priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other CF clinical factors, exhaled breath samples were collected from 18 subjects with CF, with some experiencing PEx and others serving as a baseline. Exhaled breath was collected in Tedlar bags during tidal breathing and cryotransferred to headspace vials for VOC analysis by solid phase microextraction coupled to gas chromatography-mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator treatment (HEMT), and the need for inhaled tobramycin) were also explored. Two volatile aldehydes (octanal and nonanal) were upregulated in patients not taking the HEMT. VOCs correlating to potential confounding variables were removed and then analyzed by regression for significant correlations with FEV1pp measurements. Interestingly, the VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowestp-value when comparing subjects at baseline and during PEx. Other VOCs that were differentially expressed due to PEx that were identified in this study include durene, 2,4,4-trimethyl-1,3-pentanediol 1-isobutyrate and 5-methyltridecane. Receiver operator characteristic curves were developed and showed 3,7-dimethyldecane had higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that VOCs in exhaled breath may be a rich source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.
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Fibrose Cística , Compostos Orgânicos Voláteis , Testes Respiratórios/métodos , Fibrose Cística/diagnóstico , Humanos , Pulmão/metabolismo , Projetos Piloto , Compostos Orgânicos Voláteis/análiseRESUMO
Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.
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16,16-Dimetilprostaglandina E2/uso terapêutico , Síndrome Aguda da Radiação/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Plaquetas/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Transtornos Hemorrágicos/tratamento farmacológico , Lisinopril/uso terapêutico , Megacariócitos/efeitos dos fármacos , Trombocitopenia/tratamento farmacológico , Trombopoese/efeitos dos fármacos , Síndrome Aguda da Radiação/complicações , Animais , Plaquetas/efeitos da radiação , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Proteína C-Reativa/análise , Radioisótopos de Césio , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/efeitos da radiação , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/efeitos da radiação , Feminino , Raios gama/efeitos adversos , Transtornos Hemorrágicos/etiologia , Megacariócitos/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Selectina-P/análise , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos da radiação , Fator Plaquetário 4/análise , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/etiologia , Trombocitopenia/etiologia , Trombopoese/efeitos da radiação , Irradiação Corporal Total , Fator de von Willebrand/análiseRESUMO
Superfluid 3He, with unconventional spin-triplet p-wave pairing, provides a model system for topological superconductors, which have attracted significant interest through potential applications in topologically protected quantum computing. In topological insulators and quantum Hall systems, the surface/edge states, arising from bulk-surface correspondence and the momentum space topology of the band structure, are robust. Here we demonstrate that in topological superfluids and superconductors the surface Andreev bound states, which depend on the momentum space topology of the emergent order parameter, are fragile with respect to the details of surface scattering. We confine superfluid 3He within a cavity of height D comparable to the Cooper pair diameter ξ0. We precisely determine the superfluid transition temperature Tc and the suppression of the superfluid energy gap, for different scattering conditions tuned in situ, and compare to the predictions of quasiclassical theory. We discover that surface magnetic scattering leads to unexpectedly large suppression of Tc, corresponding to an increased density of low energy bound states.
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The cellular mechanisms altered during brain wiring leading to cognitive disturbances in neurodevelopmental disorders remain unknown. We have previously reported altered cortical expression of neurodevelopmentally regulated synaptic markers in a genetic animal model of schizophrenia-relevant behavioral features, the Roman-High Avoidance rat strain (RHA-I). To further explore this phenotype, we looked at dendritic spines in cortical pyramidal neurons, as changes in spine density and morphology are one of the main processes taking place during adolescence. An HSV-viral vector carrying green fluorescent protein (GFP) was injected into the frontal cortex (FC) of a group of 11 RHA-I and 12 Roman-Low Avoidance (RLA-I) male rats. GFP labeled dendrites from pyramidal cells were 3D reconstructed and number and types of spines quantified. We observed an increased spine density in the RHA-I, corresponding to a larger fraction of immature thin spines, with no differences in stubby and mushroom spines. Glia cells, parvalbumin (PV) and somatostatin (SST) interneurons and surrounding perineuronal net (PNN) density are known to participate in FC and pyramidal neuron dendritic spine maturation. We determined by stereological-based quantification a significantly higher number of GFAP-positive astrocytes in the FC of the RHA-I strain, with no difference in microglia (Iba1-positive cells). The number of inhibitory PV, SST interneurons or PNN density, on the contrary, was unchanged. Results support our belief that the RHA-I strain presents a more immature FC, with some structural features like those observed during adolescence, adding construct validity to this strain as a genetic behavioral model of neurodevelopmental disorders.
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Esquizofrenia , Animais , Astrócitos , Espinhas Dendríticas , Lobo Frontal , Masculino , Microglia , Células Piramidais , Ratos , Esquizofrenia/genéticaRESUMO
AIM: Investigate changes in alcohol use and related harm using the first multisite, controlled, longitudinal study of Managed Alcohol Programs (MAPs). MAPs provide regular doses of alcohol, accommodation, social supports and healthcare to unstably housed people with alcohol dependence. METHODS: A multisite, quasi-experimental, longitudinal study was conducted in day centres, shelters and residential programs for unstably housed people. There were 59 MAP participants from six Canadian cities and 116 local controls. Self-reported alcohol consumption and harms were assessed at 0-2, 6 and 12 months. Liver function test results were accessed for MAP participants. RESULTS: Both groups had similar reductions in mean drinks per day (MAP: -8.11; controls: -8.54 controls, P < 0.001) and days drinking per month (MAP: -2.51 days, P < 0.05; control: -4.81 days, P = 0.0001) over 6--12 months. Both reduced non-beverage alcohol consumption. MAP participants reported significantly fewer harms at both 0-2 and 6 months than controls. MAP participants had similar total consumption to controls, but spread out over more days (25.41 versus 19.64 days per month, P = 0.001). After leaving a MAP, participants' liver status deteriorated, with increases in both aspartate transaminase and bilirubin levels. MAP sites with effective policies on outside drinking drank less and had fewer harms. CONCLUSION: MAP participants drank less hazardously than controls, especially with effective management of non-MAP drinking. Reductions in alcohol use and harms occurred for both groups, although MAP participants reported fewer harms at 0-6 months. Departing an MAP was associated with deterioration in liver status. Although providing stable housing, MAPs did not worsen health or increase alcohol use.
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Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoolismo/reabilitação , Redução do Dano , Avaliação de Programas e Projetos de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/tendências , Alcoolismo/epidemiologia , Canadá/epidemiologia , Estudos de Casos e Controles , Cidades/epidemiologia , Etanol/administração & dosagem , Feminino , Habitação , Humanos , Testes de Função Hepática , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Apoio SocialRESUMO
OBJECTIVES: This study investigated the effects of induced mental fatigue on the performance of Australian football (AF) specific skills amongst amateur AF players. DESIGN: Randomised cross over trial. METHODS: Twenty-five amateur AF players performed a series of standardised tests from the Australian Football League (AFL) Draft Combine after completing a 30-min Stroop test (mental fatigue condition) or 30-min control condition. The AFL Draft Combine tests included the standing vertical jump test, running vertical jump test, agility test, 20m sprint, Matthew Lloyd clean hands test, Brad Johnson goal kicking test and a Yo-Yo Intermittent Recovery Level 1 (Yo-Yo IR1) test. RESULTS: The Stroop test score decreased during the Stroop test (first five trials: mean=84.7, SD=3.5; last five trials: mean=82.2, SD=5.0, p=0.03). The Yo-Yo IR1 test (mental fatigue: median=920m, IQR=400; control: median=1040m, IQR=760; p=0.03) and Brad Johnson goalkicking test (mental fatigue: median=19.0, IQR=5.0; control: median=25.0, IQR=10.0, p=0.048) were negatively affected by mental fatigue. No other Draft Combine tests demonstrated a negative affect from mental fatigue. CONCLUSIONS: Mental fatigue had a detrimental influence on the performance of AF specific skills. The findings may have implications for AF players who are required to sustain attention and concentration for prolonged periods before and during matches.
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Desempenho Atlético , Fadiga Mental , Resistência Física , Desempenho Físico Funcional , Esportes , Teste de Stroop , Humanos , Masculino , Adulto Jovem , Desempenho Atlético/fisiologia , Austrália , Cognição/fisiologia , Estudos Cross-Over , Fadiga Mental/fisiopatologia , Destreza Motora , Movimento/fisiologia , Teste de Stroop/estatística & dados numéricos , Fatores de TempoRESUMO
BACKGROUND: The homeless face significant barriers accessing dental care. Community-centred dental clinics might provide more accessible care to this group. This descriptive epidemiological study aimed to measure oral health perceptions and client satisfaction among homeless and similarly disadvantaged adults receiving community-centred dental care. METHODS: A sample of 79 clients attending St Patrick's Oral Health Clinic completed Locker's Global Oral Health Item, the Oral Health Impact Profile 14 and the Client Satisfaction Questionnaire 4. RESULTS: High levels of satisfaction with St Patrick's Oral Health Clinic were based on positive staff attitudes, low cost, time effectiveness and staff sensitivity to anxiety. Ideas for improvement included shorter treatment waiting lists, offering additional treatment types and better communication and advertisement of the service. Compared to the general Australian population, participants reported a relatively poor self-perception of oral health and a high prevalence and severity of oral health impacts. CONCLUSIONS: Participants experienced significant personal and social impacts due to their oral conditions. High levels of client satisfaction reflect the value of community-centred dental care for this group. An understanding of factors influencing satisfaction might be useful for similar services providing oral care to homeless and similarly disadvantaged groups.
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Clínicas Odontológicas , Saúde Bucal , Adulto , Austrália/epidemiologia , Humanos , Satisfação do Paciente , Percepção , Satisfação PessoalRESUMO
The investigation of transport properties in normal liquid helium-3 and its topological superfluid phases provides insights into related phenomena in electron fluids, topological materials, and putative topological superconductors. It relies on the measurement of mass, heat, and spin currents, due to system neutrality. Of particular interest is transport in strongly confining channels of height approaching the superfluid coherence length, to enhance the relative contribution of surface excitations, and suppress hydrodynamic counterflow. Here we report on the thermal conduction of helium-3 in a 1.1 µm high channel. In the normal state we observe a diffusive thermal conductivity that is approximately temperature independent, consistent with interference of bulk and boundary scattering. In the superfluid, the thermal conductivity is only weakly temperature dependent, requiring detailed theoretical analysis. An anomalous thermal response is detected in the superfluid which we propose arises from the emission of a flux of surface excitations from the channel.
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This guideline is an update of a previous version published in 2013. In this new version, we have reflected changes in the way sexual health services are now provided by assuming an integrated Sexual Health/Sexual and Reproductive Healthcare service. There are new recommendations for online testing, female genital mutilation (FGM), chemsex and considerations for transgender (and non-binary) individuals. Previous versions rather assumed a cis-gender clientele and so we have taken a more mechanistic approach to sex and risk without assuming gender identification. We have updated our gender terminology in line with the British Association for Sexual Health and HIV 'sexual health standards for trans, including non-binary, people' although have retained the terminology of 'men' and 'women' in a few cases where it related to other guidelines, e.g. human papillomavirus vaccination and FGM.
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Guias como Assunto , Infecções por HIV/diagnóstico , Anamnese/normas , Encaminhamento e Consulta/normas , Comportamento Sexual , Minorias Sexuais e de Gênero/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/diagnóstico , Adulto , Feminino , Humanos , Masculino , Saúde Sexual , Minorias Sexuais e de Gênero/psicologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Resultado do Tratamento , Reino UnidoRESUMO
Considering that recumbency can lead to a change in localization, detectability of distinct margins and thus measurement of the organs and reconstruction quality, it is of value to evaluate the effect of positioning on the objective evaluation of abdominal organs in computed tomography (CT). The objective of the present study was to evaluate the effect of patient decubitus on adrenal gland CT biometry. For this purpose, 6 clinically healthy adult beagle dogs underwent CT examination in 4 recumbencies. The various adrenal gland's size measurements were performed by 2 observers. Statistical analyses revealed that repeatability and reproducibility was the highest on the ventral and right lateral recumbencies, respectively. Significant differences were found in the left adrenal gland's length between the different positions (P < 0.001) and the left adrenal gland's width of the cranial pole measured in the dorsal plane (P < 0.04). The measurements on the parasagittal images differed significantly for the left adrenal length (P = 0.01), cranial pole height (P = 0.03), the right adrenal gland's lateral limb's length (P = 0.05) and medial limb's caudal poles height (P < 0.01). The caudal pole height of the right adrenal gland's medial limb was significantly different (P < 0.01) in all positions on the transverse images. In addition, the adrenal position differed significantly, except for the left adrenal gland relative to the nearest renal vessel (P = 0.1). According to these results, it is recommended to perform a CT of adrenal glands always in the same recumbency. If adrenal glands are evaluated on images taken in various recumbencies, we suggest relying on the measurements made on transverse plane images.
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Glândulas Suprarrenais/diagnóstico por imagem , Cães/anatomia & histologia , Posicionamento do Paciente/veterinária , Tomografia Computadorizada por Raios X/veterinária , Animais , Feminino , Masculino , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear. METHODS: All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien-Dindo classification (grades 0-V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan-Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination. RESULTS: Some 1100 patients were included, with a median age of 69 (range 28-92) years; 48·1 per cent had stage III disease and cancer recurred in 428 patients (38·9 per cent). Complications of grade III or higher occurred in 244 patients (22·2 per cent). The most common complications were pulmonary (29·9 per cent), with a 13·0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10·0 and 9·6 per cent respectively. Patients with a grade III-IV leak did not have significantly reduced overall survival compared with those who had grade 0-I complications. However, patients with grade III-IV non-leak-related complications had reduced median overall survival (19·7 versus 42·7 months; P < 0·001) and disease-free survival (18·4 versus 36·4 months; P < 0·001). Cox regression analysis identified age, tumour stage, resection margin and grade III-IV non-leak-related complications as independent predictors of poor overall and disease-free survival. CONCLUSION: Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival.
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Neoplasias Esofágicas/cirurgia , Recidiva Local de Neoplasia/mortalidade , Complicações Pós-Operatórias/mortalidade , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/mortalidade , Intervalo Livre de Doença , Inglaterra/epidemiologia , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/mortalidadeRESUMO
INTRODUCTION: Repair of complex ventral hernia presents a significant challenge plagued by high morbidity and recurrence. Recent studies have demonstrated significant benefits achievable with preoperative Botulinum Toxin A (BTA) chemical component paralysis to the abdominal wall muscles, facilitating primary closure of complex ventral hernia defects. However, transversus abdominis is known to play an integral role in truncal stability, and its paralysis can result in unwanted physiological changes. This is the first study to report on selective administration of preoperative BTA to internal and external oblique muscles only, thus sparing transversus abdominis from paralysis. METHODS: This is a prospective observational study of 46 patients who underwent either selective two-layer or standard three-layer abdominal wall muscle BTA injection prior to elective laparoscopic ventral hernia repair. Serial abdominal CT imaging was performed to compare defect size and length of the lateral abdominal musculature. RESULTS: 46 patients received preoperative BTA injections (23 in each group). A comparison of gains achieved from chemical component paralysis demonstrated no statistically significant difference between the two groups. Fascial closure was achieved in all cases, with no post-operative sequelae of abdominal hypertension. There are no hernia recurrences to date. CONCLUSION: Preoperative selective muscle chemical component paralysis is an effective technique to counteract the chronic muscle retraction observed in large ventral hernias. Transversus abdominis plays a significant role in truncal and spinal stability, and sparing it from paralysis preserves an important component of abdominal wall physiology and does not detract from the ability to primarily close complex defects.