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Posterior spinal instrumentation and fusion with pedicle screws inserted by free-hand technique and controlled by multimodal intraoperative monitoring is the most common technique in adolescent idiopathic scoliosis surgery. Pneumothorax is a described complication of this kind of procedure. Triggered electromyography is used to identify pedicle wall breakthrough and prevent neurological injuries. We report 2 clinical cases in which unilateral decrease in triggered electromyography values associate with ipsilateral pneumothorax. Postoperative chest radiographs need to be done in order to diagnose a pneumothorax. However, routinely performing a chest radiograph has been questioned because of the low incidence of this surgical complication. As a result of the association described in this article, we consider that when a unilateral decrease in triggered electromyography values is detected, a hidden pneumothorax should be suspected and ruled out.
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AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.
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Biópsia Guiada por Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.
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Insuficiência Cardíaca , Coração Auxiliar , Adulto , Estudos de Viabilidade , Terapia Genética , Vetores Genéticos/genética , Insuficiência Cardíaca/terapia , Humanos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
BACKGROUND AND PURPOSE: The purpose of this study is to identify which variables may have a significant impact in mid-term survivorship following hip arthroscopy. METHODS: This a single-centre single-surgeon retrospective study including 102 patients who underwent a hip arthroscopy procedure between August 2007 and October 2011. Each subject completed three questionnaires at final follow- up: Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sport (HOS-S) and Modified Harris Hip Score (m-HHS). RESULTS: Thirty-nine patients (40 hips) were finally included in our study. Mean age was 43.1 ± 9.9 years with a three-year minimum follow-up (75.43 ± 25.2 months). Younger patients and those with a shorter duration of symptoms obtained significantly higher HOS-S and m-HSS scores. Patients who had undergone previous lumbar spinal surgery obtained significantly worse HOS-ADL scores. Patient acceptable symptom state (PASS) was achieved in 23 patients (57.5%) for m-HHS, 22 patients (55%) for HOS-ADL and 25 patients for HOS-S scores. No major complication was observed. Only four patients had minor complications. Mean survival time was 97.1 months (95% CI, 85.1 to 109.1 months), with a survival at 8 years of 69% (95% CI, 53% to 85%). CONCLUSIONS: Our findings suggest that hip arthroscopy is a safe procedure with acceptable functional outcomes after a long follow-up. Care should be taken when treating patients with prior lumbar surgery. LEVEL OF EVIDENCE: Level IV.
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Artroscopia , Impacto Femoroacetabular/mortalidade , Impacto Femoroacetabular/cirurgia , Osteoartrite do Quadril/mortalidade , Osteoartrite do Quadril/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). METHODS: 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. RESULTS: Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. CONCLUSIONS: Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.
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Neoplasias da Mama/cirurgia , Hiperalgesia/diagnóstico , Hiperestesia/diagnóstico , Mastectomia/efeitos adversos , Neuralgia/diagnóstico , Dor Pós-Operatória/diagnóstico , Idoso , Estudos de Coortes , Feminino , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Hiperestesia/tratamento farmacológico , Hiperestesia/etiologia , Hiperestesia/fisiopatologia , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Medição da Dor , Limiar da Dor/fisiologia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Sensação/fisiologia , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
OBJECTIVE: To describe the characteristics and evolution of deep surgical site infection following thoracolumbar instrumented spinal surgery (DSITIS) in our centre over a period of ten years. MATERIAL AND METHOD: Descriptive retrospective study. Patient data (epidemiological/health status), surgical data, infection characteristics/presentation, isolated microorganisms, required surgical debridements, implant removal and major complications linked to infection were evaluated. RESULTS: We included 110 patients (80 females). Median follow-up after infection diagnosis was 3.6years. Adolescent idiopathic scoliosis, adult deformity and degenerative lumbar stenosis were the most frequent aetiologies. Sixty-two percent of the patients had at least one clinical feature that made them prone to infection. Infection presentation was early (0-3months from first surgery) in 60.4% of the cases, delayed (3-24months) in 11.7%, and late (more than 24months) in 27%. All patients were treated by surgical debridement. Twenty-five percent needed more than one surgical debridement. Implants were removed in 46% of the patients (71% in the first surgical debridement). The most frequent isolated microorganisms were coagulasa-negative Staphylococcus, Propionibacterium acnes and Enterococcus. Major complications appeared in 15% of the patients, and 88% of them required major surgeries. CONCLUSIONS: Late DSITIS is more frequent than previously reported. Skin microorganisms predominate among the DSITIS culprits. DSIITS produce a high rate of major complications that usually require major surgery for treatment.
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Escoliose/cirurgia , Estenose Espinal/cirurgia , Coluna Vertebral/anormalidades , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Desbridamento/estatística & dados numéricos , Remoção de Dispositivo/estatística & dados numéricos , Enterococcus/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propionibacterium acnes/isolamento & purificação , Estudos Retrospectivos , Pele/microbiologia , Staphylococcus/isolamento & purificação , Infecção da Ferida Cirúrgica/complicações , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo , Adulto JovemRESUMO
Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial-mesenchymal transition (EMT) and resistance to chemotherapeutics. We found that recapitulation of the fibrotic rigidities found in pancreatic cancer tissues promote elements of EMT, including increases in vimentin expression, decreases in E-cadherin expression, nuclear localisation of ß-catenin, YAP and TAZ and changes in cell shape towards a mesenchymal phenotype. We also report that stiffness induces chemoresistance to paclitaxel, but not to gemcitabine, both commonly used therapeutics, suggesting that environmental rigidity underlies an aspect of chemoresistance.
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BACKGROUND: Pain is associated with affective, cognitive and sensory dysfunction. Animal models can be used to observe ethologically relevant behaviours such as thigmotaxis, giving insight into how ongoing sensory abnormalities influence natural rodent behaviours. The amygdala is a complex group of nuclei implicated in the integration and generation of emotional behavioural responses, including those associated with pain, and a region known as the central amygdala is particularly associated with generation of behavioural responses, due to its links to the descending pain modulation pathways; as such, study of amygdalar c-Fos immunoreactivity can help identify the neuronal circuits involved. METHOD: This study investigated changes in both nociceptive evoked responses and open field behaviour following spinal nerve transection (SNT) in male Wistar rats, and attempted to correlate these with changes in central amygdala c-Fos immunoreactivity. RESULTS: Fourteen days after SNT, mechanical hypersensitivity was present in the hind paw ipsilateral to site of injury. Thigmotactic behaviour was significantly increased in both SNT and sham surgery animals, with c-Fos immunoreactivity in the central amygdala significantly greater in SNT animals compared to both sham and naive groups. Activation was greatest in the capsular and lateral subnuclei of the central amygdala, and in the caudal-most regions. There was a strong correlation between thigmotactic behaviour and central amygdala activation following SNT surgery not seen in sham animals suggesting a role for the amygdala in behavioural responses to peripheral nerve injury. CONCLUSIONS: This study provides evidence to support the role of the amygdala in thigmotactic open field behaviour following SNT. WHAT DOES THIS STUDY ADD?: Thigmotaxis and amygdala activation are positively correlated in rats following spinal nerve transection. Behavioural changes seen in sham animals did not correlate with amygdala activation, suggesting amygdala activation is related to nociceptive input. Evoked measures, such as hindpaw withdrawal, are not correlated with either thigmotaxis or amygdala activation, emphasizing the importance of complex behaviours when studying pain.
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Núcleo Central da Amígdala/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Nervos Espinhais/lesões , Animais , Comportamento Animal , Comportamento Exploratório , Masculino , Neuralgia/etiologia , Neuralgia/psicologia , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/psicologia , Ratos , Ratos WistarRESUMO
PURPOSE: Quality of life in women receiving adjuvant endocrine therapy for breast cancer (BC) may be impaired by hot flushes and night sweats. The cool pad pillow topper (CPPT) is a commercial product, promoted to improve quality of sleep disrupted by hot flushes. This study aimed to identify if the CPPT reduces severity of sleep disturbance by minimising effects of hot flushes. METHODS: This randomised phase II trial, recruited women with BC, on adjuvant endocrine therapy, experiencing hot flushes and insomnia. Participants were randomised (stratified by baseline sleep efficiency score (SES) and menopausal status) to the intervention arm (CPPT + standard care) or control arm (standard care). Participants completed Hospital Anxiety and Depression Scale and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires and fortnightly sleep/hot flush diaries (where responses were averaged over 2-week periods). The primary endpoint was change in average SES from -2 to 0 weeks to 2 to 4 weeks. RESULTS: Seventy-four pre- (68.9 %) and post-menopausal (31.1 %) women were recruited. Median age was 49.5 years. Endocrine therapies included tamoxifen (93.2 %). Median SES at weeks 2 to 4 improved in both arms but the increase on the intervention arm was almost twice that on the control arm (p = 0.024). There were significantly greater reductions in hot flushes and HADS depression in the intervention arm (p = 0.09 and p = 0.036, respectively). There were no significant differences in FACT-B or HADS anxiety. CONCLUSION: This study supports the use of the CPPT as an aid to reduce sleep disturbance and the frequency/severity of hot flushes.
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Roupas de Cama, Mesa e Banho , Neoplasias da Mama/complicações , Crioterapia/instrumentação , Fogachos/terapia , Distúrbios do Início e da Manutenção do Sono/terapia , Adulto , Antineoplásicos Hormonais/efeitos adversos , Ansiedade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Crioterapia/métodos , Depressão , Feminino , Fogachos/induzido quimicamente , Fogachos/psicologia , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/psicologia , Inquéritos e Questionários , Sudorese , Tamoxifeno/efeitos adversos , Resultado do TratamentoRESUMO
We have investigated if immunotherapy against human papilloma virus (HPV) using a viral gene delivery platform to immunize against HPV 16 genes E6 and E7 (Ad5 [E1-, E2b-]-E6/E7) combined with programmed death-ligand 1 (PD-1) blockade could increase therapeutic effect as compared to the vaccine alone. Ad5 [E1-, E2b-]-E6/E7 as a single agent induced HPV-E6/E7 cell-mediated immunity. Immunotherapy using Ad5 [E1-, E2b-]-E6/E7 resulted in clearance of small tumors and an overall survival benefit in mice with larger established tumors. When immunotherapy was combined with immune checkpoint blockade, an increased level of anti-tumor activity against large tumors was observed. Analysis of the tumor microenvironment in Ad5 [E1-, E2b-]-E6/E7 treated mice revealed elevated CD8(+) tumor infiltrating lymphocytes (TILs); however, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1(+) TILs. When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8(+) TILs at the same level but a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1(+) TILs providing a mechanism by which combination therapy favors a tumor clearance state and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials.
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Antígeno B7-H1/biossíntese , Vacinas Anticâncer/uso terapêutico , Imunoterapia , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/imunologia , Proteínas E7 de Papillomavirus/imunologia , Proteínas Repressoras/imunologia , Infecções Tumorais por Vírus/terapia , Neoplasias do Colo do Útero/terapia , Animais , Apoptose/genética , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Terapia Combinada , Vírus Defeituosos/genética , Vírus Defeituosos/imunologia , Feminino , Regulação da Expressão Gênica , Humanos , Imunoglobulina G/imunologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Ratos , Proteínas Repressoras/genética , Linfócitos T Citotóxicos/imunologia , Microambiente Tumoral , Infecções Tumorais por Vírus/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Leafmining flies (Diptera: Agromyzidae) can be serious economic pests of horticultural crops. Some genera such as Liriomyza are particularly problematic with numerous species, some of which are highly polyphagous (wide host range), which can only be confidently identified morphologically from adult males. In our study, DNA barcoding was employed to establish new locality records of the vegetable leafminer fly, Liriomyza sativae, from the islands of Torres Strait (Queensland, Australia) and the central highlands of Papua New Guinea (PNG). These records represent significant range extensions of this highly invasive plant pest. Specimens of immature leafminers (from leaf mines) were collected over a 5-year period during routine plant health surveys in ethanol or on FTA® filter paper cards, both methods proved effective at preserving and transporting insect DNA under tropical conditions, with FTA cards possessing some additional logistical benefits. Specimens were identified through sequencing two sections of the cytochrome oxidase I gene and the utility of each was assessed for the identification of species and intra-specific genetic lineages. Our study indicates that multiple haplotypes of L. sativae occur in PNG, while a different haplotype is present in the Torres Strait, with genetic regionalization between these areas apart from a single possible instance - one haplotype 'S.7' appears to be common between these two regions - interestingly this has also been the most common haplotype detected in previous studies of invasive L. sativae populations. The DNA barcoding methods employed here not only identified multiple introductions of L. sativae, but also appear generally applicable to the identification of other agromyzid leafminers (Phytomyzinae and Agromyzinae) and should decrease the likelihood of potentially co-amplifying internal hymenopteran parasitoids. Currently, L. sativae is still not recorded from the Australian mainland; however, further sampling of leafminer flies from Northern Australia and surrounding areas is required, as surveillance for possible Liriomyza incursions, as well as to characterize endemic species with which Liriomyza species might be confused.
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DNA/genética , Dípteros/genética , Espécies Introduzidas , Animais , Dípteros/fisiologia , Larva/genética , Larva/fisiologia , Masculino , Papua Nova Guiné , QueenslandRESUMO
BACKGROUND: Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA and pose a potential for misdiagnosis. OBJECTIVES: To investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities and VWF genotypes. PATIENTS/METHODS: Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and VWF sequence. RESULTS: Four cases had VWF:Ag < 3 IU dL(-1) and VWF mutations consistent with Type 3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type 1 VWD (VWD1) (n = five cases and one control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n = 1 case). One control had VWF:Ag < 30 IU dL(-1) and seven patients (four cases and three controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. CONCLUSIONS: These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy.
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Coagulação Sanguínea/genética , Fator VIII/genética , Hemofilia A/genética , Mutação , Fator de von Willebrand/genética , Adolescente , Adulto , Biomarcadores/sangue , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Criança , Análise Mutacional de DNA , Fator VIII/metabolismo , Predisposição Genética para Doença , Hemofilia A/sangue , Hemofilia A/diagnóstico , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/genética , Heterozigoto , Homozigoto , Humanos , Masculino , Fenótipo , Valor Preditivo dos Testes , Ligação Proteica , Estados Unidos , Adulto Jovem , Fator de von Willebrand/metabolismoRESUMO
This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.
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Anticorpos/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Transplante de Coração , Inflamação/patologia , Miocardite/patologia , Fenótipo , Adulto , Biópsia , Capilares/metabolismo , Capilares/patologia , Estudos de Casos e Controles , Complemento C4b/metabolismo , Europa (Continente) , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Projetos Piloto , Estudos Retrospectivos , Doadores de TecidosRESUMO
BACKGROUND: Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most frequent neurological complication of HIV disease. Among the probable mechanisms underlying HIV-SN are neurotoxicity induced by the HIV glycoprotein gp120 and antiretroviral therapies (ART). Since HIV-SN prevalence remains high in patients who have not been exposed to toxic ART drugs, here we focused on gp120-mediated mechanisms underlying HIV-SN. METHODS: We hypothesized that a direct gp120-sensory neurone interaction is not the cause of neurite degeneration; rather, an indirect interaction of gp120 with sensory neurones involving macrophages underlies axonal degeneration. Rat dorsal root ganglion (DRG) cultures were used to assess gp120 neurotoxicity. Rat bone marrow-derived macrophage (BMDM) cultures and qPCR array were used to assess gp120-associated gene expression changes. RESULTS: gp120 induced significant, but latent onset, neurite degeneration until 24 h after application. gp120-neurone interaction occurred within 1 h of application in <10% of DRG neurones, despite neurite degeneration having a global effect. Application of culture media from gp120-exposed BMDMs induced a significant reduction in DRG neurite outgrowth. Furthermore, gp120 significantly increased the expression of 25 cytokine-related genes in primary BMDMs, some of which have been implicated in other painful polyneuropathies. The C-C chemokine receptor type 5 (CCR5) antagonist, maraviroc, concentration-dependently inhibited gp120-induced tumour necrosis factor-α gene expression, indicating that these effects occurred via gp120 activation of CCR5. CONCLUSIONS: Our findings highlight macrophages in the pathogenesis of HIV-SN and upstream modulation of macrophage response as a promising therapeutic strategy.
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Proteína gp120 do Envelope de HIV/toxicidade , HIV-1 , Macrófagos/patologia , Síndromes Neurotóxicas/patologia , Células Receptoras Sensoriais/patologia , Animais , Técnicas de Cultura de Células/métodos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Degeneração Neural/patologia , Doenças do Sistema Nervoso Periférico , Reação em Cadeia da Polimerase/métodos , Ratos , Ratos Wistar , Células Receptoras Sensoriais/efeitos dos fármacosRESUMO
Pain influences many aspects of daily living and effective analgesics should reinstate normal spontaneous daily behaviours. Experiments are described herein which show that the innate, spontaneous behaviour of burrowing by rats, which can be simply and objectively assessed by measuring the amount of gravel left in a hollow tube 1 h after presentation to the rat, is reduced by peripheral nerve injury (tibial nerve transection (TNT), L5 spinal nerve transection (SNT) and partial sciatic nerve ligation (PSNL)) and also following inflammation induced by intra-plantar injection of Complete Freund's Adjuvant (CFA). Gabapentin (100 mg/kg sc) but not at 30 mg/kg sc significantly reduced burrowing activity in naive rats. All peripheral nerve injuries and CFA reduced burrowing compared with shams and rats naive to surgery. The level of mechanical hypersensitivity in rats with peripheral nerve injury did not correlate with the deficit in burrowing indicating that different parameters of the holistic pain experience are measured in these paradigms. Gabapentin at 30 mg/kg sc, but not 100 mg/kg sc, reversed the deficit in burrowing induced by TNT and ibuprofen (30 mg/kg sc) reversed the effect of CFA on burrowing. These experiments show that measurement of burrowing is a simple, objective assay of innate rodent behaviour affected by pain that is ethologically relevant to the rat, does not rely wholly on evoking a reflex and can dissociate a selective analgesic dose of gabapentin from one inducing motor impairment in the same animal.
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Comportamento Animal/fisiologia , Inflamação/psicologia , Dor/psicologia , Traumatismos dos Nervos Periféricos/psicologia , Aminas/farmacologia , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Interações Medicamentosas , Gabapentina , Hiperalgesia/etiologia , Hiperalgesia/psicologia , Ibuprofeno/farmacologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Dor/etiologia , Medição da Dor , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Meio Social , Nervos Espinhais/lesões , Nervo Tibial/lesões , Ácido gama-Aminobutírico/farmacologiaRESUMO
OBJECTIVES: To assess the clinical validity of two new recently described parameters (spinal-sacral angle (SSA) and spinal inclination angle (SIA) in adult scoliosis (AS) for evaluating the spinal-pelvic sagittal profile, as well as their still undefined role in AS. MATERIAL AND METHOD: A non-concurrent prospective radiographic and clinical study was conducted on 59 primary surgeries of AS (Cobb>40°), with a minimum of 2 years follow-up. The available X-rays and health questionnaires of 49 patients were used in the study. The changes in X-ray parameters after surgery were evaluated (Wilcoxon test), as well as the correlations as regards the clinical-radiography-age parameters (Spearman test and multiple linear regression). RESULTS: The median post-surgical follow-up was 8.5 years, and the median age of the patients was 49.5 years. There was a statistically significant change with the surgery in the SSA and SIA (less than 5° in both), thoracic kyphosis, lumbar lordosis (LL), pelvic rotation, sagittal balance (SB) and frontal Cobb. There was no correlation between pain and SSA-ST. There was a significant relationship between activity and SSA, ST, LL, SB, and age. After the multivariate analysis only age (not SSA or SIA) remained as a possible predictor of lower activity. DISCUSSION: When frontal deformity predominates, the sagittal radiographic parameters, including the newest angles, although they have an influence patient activity when analysed individually, they lose this influence when they are analysed together and with other clinical parameters. CONCLUSIONS: The SSA and SIA hardly change with surgery. They only correlate with activity, but cannot be considered predictors of this. Thus they do seem to be useful measurements in AS.
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Escoliose/diagnóstico por imagem , Fusão Vertebral , Adulto , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Qualidade de Vida , Radiografia , Escoliose/patologia , Escoliose/cirurgia , Resultado do TratamentoRESUMO
Patellar tumours are rare. They typically appear in young patients, and present with a non-specific pain in the knee. Giant cell tumour (GCT) are benign, but locally aggressive. Although they are usually found around the knee (40-60%), those affecting the patella have been classically described in the literature as uncommon. We describe the case of a 19 year old male complaining of pain in his knee, whose clinical examination suggested a meniscal tear. Plain radiological examination, as well as MRI, revealed a well circumscribed lytic lesion within the patella. The patient underwent arthroscopic surgery, during which an incisional biopsy was performed. Following pathology reports, which confirmed the suspected GCT, definitive surgery was performed. At 56 months after the surgery the patient remains asymptomatic and free of disease.
Assuntos
Neoplasias Ósseas/diagnóstico , Tumor de Células Gigantes do Osso/diagnóstico , Patela , Humanos , Masculino , Patela/diagnóstico por imagem , Patela/patologia , Radiografia , Adulto JovemRESUMO
The likelihood of difficult airway in thoracic surgery increases in the presence of associated cancer of the pharynx or larynx. The difficulty is greater when a double lumen tube must be inserted in these conditions, and various newly developed optical devices offer solutions for managing such cases. We report on 2 patients with expected difficult airway who were scheduled for lung resection. In both cases, intubation was accomplished through the AirTraq laryngoscope while the patient remained awake. Awake patient tolerance is facilitated by this laryngoscope, because the tube can be inserted without changing the position of the tongue or placing pressure on the vallecula.
Assuntos
Manuseio das Vias Aéreas/métodos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Laringoscópios , Idoso , Desenho de Equipamento , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The number of patients suffering from a diabetic foot syndrome is increasing. In many cases large plantar or heel defects can only be reconstructed by using a free flap. The free parascapular flap is an alternative to free muscle flaps in the reconstruction of plantar or heel defects. Donor site morbidity is low. Autologous bypass reconstruction or an angioplasty can increase extremity perfusion. PATIENTS AND OPERATIONS: 52 patients with a diabetic foot syndrome have been reconstructed since 2007. 23 of them required a free tissue transfer. On average these patients were 68.7 years of age. A parascapular flap was used in 15 cases, a latissimus dorsi flap with a skin graft in 4 cases, a gracilis muscle flap with a skin graft in 3 cases. In one case a free instep flap of the contralateral foot, which had to be amputated, was used. In 13 cases the flap was anastomosed to the autologous bypass, in one case an AV loop was used. RESULTS: 22 flaps healed primarily. Only 1 patient was not able to walk at discharge. There was one flap loss. 4 patients required an amputation later on due to bypass failure or infection. 2 patients died due to cardiac arrest at the rehabilitation clinic. CONCLUSION: If the correct indication is met, free flaps can prevent diabetes-derived amputations of the lower limb. The parascapular flap can be used for plantar and heel defects. Flap harvesting is quick due to the constant vascular anatomy. The donor site morbidity is low. Reconstruction requires revascularisation in an interdisciplinary setting including vascular surgeons and radiologists. Limb salvage reduces mortality and improves quality of life. Revascularisation and reconstruction should best be done in a single surgical procedure.