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1.
J Craniofac Surg ; 34(1): 302-305, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35994750

RESUMO

Craniostenosis is a morphological anomaly affecting about 0.5 of 1000 births and one third of the cases are of genetic origin. Among the syndromes responsible for craniostenosis, there is the Saethre-Chotzen syndrome due to a mutation of the TWIST 1 gene located on chromosome 7. This polymalformative syndrome classically includes a particular morphology of the auricles. The penetrance is variable and results in a phenotypic variability at the origin of "Saethre-Chotzen like" clinical pictures for which the TWIST 1 gene mutation is sometimes not found. Recently, the TCF 12 gene has been implicated in some of these cases. Among the multiple facial malformations, we have carefully examined the particular morphology of the auricle of these patients. The authors found several abnormalities in patients with a TCF 12 gene mutation, namely a thickened and hammered upper pole of the helix, a narrow concha without crux cymbae and a thickened lobe. These morphological features may guide the diagnosis and allow an earlier search for a TCF 12 gene mutation.


Assuntos
Acrocefalossindactilia , Craniossinostoses , Humanos , Proteína 1 Relacionada a Twist/genética , Fatores de Transcrição/genética , Mutação , Acrocefalossindactilia/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
2.
J Immunother Cancer ; 10(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35640928

RESUMO

BACKGROUND: The phase II NIVOREN GETUG-AFU 26 study reported safety and efficacy of nivolumab in patients with metastatic clear cell renal cell carcinoma (m-ccRCC) in a 'real-world setting'. We conducted a translational-research program to determine whether specific circulating immune-cell populations and/or soluble factors at baseline were predictive of clinical outcomes in patients with m-ccRCC treated with nivolumab within the NIVOREN study. METHODS: Absolute numbers of 106 circulating immune-cell populations were prospectively analyzed in patients treated at a single institution within the NIVOREN trial with available fresh-whole-blood, using dry formulation panels for multicolor flow cytometry. In addition, a panel of 14 predefined soluble factors was quantified for each baseline plasma sample using the Meso-Scale-Discovery immunoassay. The remaining patients with available plasma sample were used as a validation cohort for the soluble factor quantification analysis. Tumor immune microenvironment characterization of all patients included in the translational program of the study was available. The association of blood and tissue-based biomarkers, with overall survival (OS), progression-free survival (PFS) and response was analyzed. RESULTS: Among the 44 patients, baseline unswitched memory B cells (NSwM B cells) were enriched in responders (p=0.006) and associated with improved OS (HR=0.08, p=0.002) and PFS (HR=0.54, p=0.048). Responders were enriched in circulating T follicular helper (Tfh) (p=0.027) and tertiary lymphoid structures (TLS) (p=0.043). Circulating NSwM B cells positively correlated with Tfh (r=0.70, p<0.001). Circulating NSwM B cells correlated positively with TLS and CD20 +B cells at the tumor center (r=0.59, p=0.044, and r=0.52, p=0.033) and inversely correlated with BCA-1/CXCL13 and BAFF (r=-0.55 and r=-0.42, p<0.001). Tfh cells also inversely correlated with BCA-1/CXCL13 (r=-0.61, p<0.001). IL-6, BCA-1/CXCL13 and BAFF significantly associated with worse OS in the discovery (n=40) and validation cohorts (n=313). CONCLUSION: We report the first fresh blood immune-monitoring of patients with m-ccRCC treated with nivolumab. Baseline blood concentration of NSwM B cells was associated to response, PFS and OS in patients with m-ccRCC treated with nivolumab. BCA-1/CXCL13 and BAFF, inversely correlated to NSwM B cells, were both associated with worse OS in discovery and validation cohorts. Our data confirms a role for B cell subsets in the response to immune checkpoint blockade therapy in patients with m-ccRCC. Further studies are needed to confirm these findings.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Células B de Memória , Nivolumabe/uso terapêutico , Microambiente Tumoral
3.
Lancet Oncol ; 23(5): 612-624, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35390339

RESUMO

BACKGROUND: We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab-ipilimumab. We therefore aimed to evaluate treatment efficacy and tolerability of nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors (VEGFR-TKIs) in patients according to tumour molecular groups. METHODS: This biomarker-driven, open-label, non-comparative, randomised, phase 2 trial included patients from 15 university hospitals or expert cancer centres in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had previously untreated metastatic clear-cell renal cell carcinoma. Patients were randomly assigned (1:1) using permuted blocks of varying sizes to receive either nivolumab or nivolumab-ipilimumab (ccrcc1 and ccrcc4 groups), or either a VEGFR-TKI or nivolumab-ipilimumab (ccrcc2 and ccrcc3 groups). Patients assigned to nivolumab-ipilimumab received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by intravenous nivolumab 240 mg every 2 weeks. Patients assigned to nivolumab received intravenous nivolumab 240 mg every 2 weeks. Patients assigned to VEGFR-TKIs received oral sunitinib (50 mg/day for 4 weeks every 6 weeks) or oral pazopanib (800 mg daily continuously). The primary endpoint was the objective response rate by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint and safety were assessed in the population who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02960906, and with the EU Clinical Trials Register, EudraCT 2016-003099-28, and is closed to enrolment. FINDINGS: Between June 28, 2017, and July 18, 2019, 303 patients were screened for eligibility, 202 of whom were randomly assigned to treatment (61 to nivolumab, 101 to nivolumab-ipilimumab, 40 to a VEGFR-TKI). In the nivolumab group, two patients were excluded due to a serious adverse event before the first study dose and one patient was excluded from analyses due to incorrect diagnosis. Median follow-up was 18·0 months (IQR 17·6-18·4). In the ccrcc1 group, objective responses were seen in 12 (29%; 95% CI 16-45) of 42 patients with nivolumab and 16 (39%; 24-55) of 41 patients with nivolumab-ipilimumab (odds ratio [OR] 0·63 [95% CI 0·25-1·56]). In the ccrcc4 group, objective responses were seen in seven (44%; 95% CI 20-70) of 16 patients with nivolumab and nine (50% 26-74) of 18 patients with nivolumab-ipilimumab (OR 0·78 [95% CI 0·20-3·01]). In the ccrcc2 group, objective responses were seen in 18 (50%; 95% CI 33-67) of 36 patients with a VEGFR-TKI and 19 (51%; 34-68) of 37 patients with nivolumab-ipilimumab (OR 0·95 [95% CI 0·38-2·37]). In the ccrcc3 group, no objective responses were seen in the four patients who received a VEGFR-TKI, and in one (20%; 95% CI 1-72) of five patients who received nivolumab-ipilimumab. The most common treatment-related grade 3-4 adverse events were hepatic failure and lipase increase (two [3%] of 58 for both) with nivolumab, lipase increase and hepatobiliary disorders (six [6%] of 101 for both) with nivolumab-ipilimumab, and hypertension (six [15%] of 40) with a VEGFR-TKI. Serious treatment-related adverse events occurred in two (3%) patients in the nivolumab group, 38 (38%) in the nivolumab-ipilimumab group, and ten (25%) patients in the VEGFR-TKI group. Three deaths were treatment-related: one due to fulminant hepatitis with nivolumab-ipilimumab, one death from heart failure with sunitinib, and one due to thrombotic microangiopathy with sunitinib. INTERPRETATION: We demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma. FUNDING: Bristol Myers Squibb, ARTIC.


Assuntos
Carcinoma de Células Renais , Nivolumabe , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Ipilimumab , Lipase , Masculino , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Sunitinibe , Microambiente Tumoral
4.
Oncologist ; 27(6): 501-511, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35278076

RESUMO

BACKGROUND: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms. Data linking BAF alterations with tumor microenvironment (TME) and efficacy of immune checkpoint inhibitors (ICI) are contradictory. The TME of SMARCA4-UT and their response to ICI are unknown. MATERIALS AND METHODS: Patients diagnosed with SMARCA4-UT in our institution were included. Immunostainings for tertiary lymphoid structures (TLS), immune cell markers, and checkpoints were assessed. Validation was performed using an independent transcriptome dataset including SMARCA4-UT, non-small cell lung cancers (NSCLC) with/without SMARCA4 mutations, and unclassified thoracic sarcomas (UTS). CXCL9 and PD-L1 expressions were assessed in NSCLC and thoracic fibroblast cell lines, with/without SMARCA4 knockdown, treated with/without interferon gamma. RESULTS: Nine patients were identified. All samples but one showed no TLS, consistent with an immune desert TME phenotype. Four patients received ICI as part of their treatment, but the only one who responded, had a tumor with a TLS and immune-rich TME. Unsupervised clustering of the validation cohort using immune cell scores identified 2 clusters associated with cell ontogeny and immunity (cluster 1 enriched for NSCLC independently of SMARCA4 status (n = 9/10; P = .001); cluster 2 enriched for SMARCA4-UT (n = 11/12; P = .005) and UTS (n = 5/5; P = .0005). SMARCA4 loss-of-function experiments revealed interferon-induced upregulation of CXCL9 and PD-L1 expression in the NSCLC cell line with no effect on the thoracic fibroblast cell line. CONCLUSION: SMARCA4-UT mainly have an immune desert TME with limited efficacy to ICI. TME of SMARCA4-driven tumors varies according to the cell of origin questioning the interplay between BAF alterations, cell ontogeny and immunity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Helicases , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Proteínas Nucleares , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias Torácicas , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , DNA Helicases/deficiência , DNA Helicases/imunologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Proteínas Nucleares/deficiência , Proteínas Nucleares/imunologia , Sarcoma/tratamento farmacológico , Sarcoma/imunologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/imunologia , Neoplasias de Tecidos Moles/patologia , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/imunologia , Neoplasias Torácicas/patologia , Fatores de Transcrição/imunologia , Microambiente Tumoral/imunologia
5.
Immunity ; 55(3): 527-541.e5, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35231421

RESUMO

The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Estruturas Linfoides Terciárias , Carcinoma de Células Renais/terapia , Feminino , Humanos , Imunoglobulina G , Neoplasias Renais/terapia , Masculino , Plasmócitos , Estruturas Linfoides Terciárias/patologia , Microambiente Tumoral
6.
Clin Cancer Res ; 27(24): 6749-6760, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34407968

RESUMO

PURPOSE: A minority of patients currently respond to single-agent immune-checkpoint blockade (ICB), and strategies to increase response rates are urgently needed. AXL is a receptor tyrosine kinase commonly associated with drug resistance and poor prognosis in many cancer types, including in clear-cell renal cell carcinoma (ccRCC). Recent experimental cues in breast, pancreatic, and lung cancer models have linked AXL with immune suppression and resistance to antitumor immunity. However, its role in intrinsic and acquired resistance to ICB remains largely unexplored. EXPERIMENTAL DESIGN: In this study, tumoral expression of AXL was examined in ccRCC specimens from 316 patients who were metastatic receiving the PD-1 inhibitor nivolumab in the GETUG AFU 26 NIVOREN trial after failure of antiangiogenic therapy. We assessed associations between AXL and patient outcomes following PD-1 blockade, as well as the relationship with various markers, including PD-L1; VEGFA; the immune markers CD3, CD8, CD163, and CD20; and the mutational status of the tumor-suppressor gene von Hippel-Lindau (VHL). RESULTS: Our results show that high AXL-expression level in tumor cells is associated with lower response rates and a trend to shorter progression-free survival following anti-PD-1 treatment. AXL expression was strongly associated with tumor-PD-L1 expression, especially in tumors with VHL inactivation. Moreover, patients with tumors displaying concomitant PD-L1 expression and high AXL expression had the worst overall survival. CONCLUSIONS: Our findings propose AXL as candidate factor of resistance to PD-1 blockade, and provide compelling support for screening both AXL and PD-L1 expression in the management of advanced ccRCC.See related commentary by Hahn et al., p. 6619.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1
7.
Cancer Immunol Res ; 9(8): 891-908, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34039653

RESUMO

The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated with poor prognosis in two cohorts of patients with ccRCC. High expression of the C4-activating enzyme C1s by tumor cells was associated with poor prognosis in three cohorts. Multivariate Cox analysis revealed that the prognostic value of C1s was independent from complement deposits, suggesting the possibility of complement cascade-unrelated, protumoral functions for C1s. Silencing of C1s in cancer cell lines resulted in decreased proliferation and viability of the cells and in increased activation of T cells in in vitro cocultures. Tumors expressing high levels of C1s showed high infiltration of macrophages and T cells. Modification of the tumor cell phenotype and T-cell activation were independent of extracellular C1s levels, suggesting that C1s was acting in an intracellular, noncanonical manner. In conclusion, our data point to C1s playing a dual role in promoting ccRCC progression by triggering complement activation and by modulating the tumor cell phenotype and tumor microenvironment in a complement cascade-independent, noncanonical manner. Overexpression of C1s by tumor cells could be a new escape mechanism to promote tumor progression.See related Spotlight by Magrini and Garlanda, p. 855. See article by Daugan et al., p. 909 (40).


Assuntos
Biomarcadores Tumorais/metabolismo , Complemento C1s/metabolismo , Complemento C4/metabolismo , Neoplasias Renais/genética , Animais , Estudos de Casos e Controles , Humanos , Camundongos , Prognóstico , Estudos Prospectivos , Transfecção
8.
J Trauma Acute Care Surg ; 89(3): e59-e63, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32467466

RESUMO

BACKGROUND: Management of critically ill patients requiring mechanical ventilation in austere environments or during disaster response is a logistic challenge. Availability of oxygen cylinders for mechanically ventilated patient may be difficult in such a context. A solution to ventilate patients requiring high fraction of inspired oxygen (FiO2) is to use a ventilator able to be supplied by a low-pressure oxygen source connected with two oxygen concentrators (OCs). We tested the Elisée 350 (ResMedBella Vista, Australia) ventilator paired with two Newlife Intensity 10 (Airsep, Ball Ground, Georgia) OCs and evaluated the delivered FiO2 across a range of minute volumes and combinations of ventilator settings. METHODS: The ventilators were attached to a test lung, OC flow was adjusted with a Certifier FA ventilator test systems from 2 to 10 L/min and injected into the oxygen inlet port of the Elisée 350. The FiO2 was measured by the analyzer integrated in the ventilator, controlled by the ventilator test system. Several combinations of ventilator settings were evaluated to determine the factors affecting the delivered FiO2. RESULTS: The Elisée 350 ventilator is a turbine ventilator able to deliver high FiO2 when functioning with two OCs. However, modifications of the ventilator settings such as an increase in minute ventilation affect delivered FiO2 even if oxygen flow is constant on the OC. CONCLUSION: The ability of two OCs to deliver high FiO2 when used with a turbine ventilator makes this method of oxygen delivery a viable alternative to cylinders to ventilate patients requiring an FiO2 of ≥80% in austere place or during disaster response. LEVEL OF EVIDENCE: Feasibility study on test bench, level V.


Assuntos
Medicina Militar/instrumentação , Oxigenoterapia/instrumentação , Respiração Artificial , COVID-19/terapia , Estado Terminal/terapia , Desenho de Equipamento , França , Humanos
9.
Nature ; 577(7791): 556-560, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942077

RESUMO

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8+ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.


Assuntos
Linfócitos B/imunologia , Imunoterapia , Sarcoma/tratamento farmacológico , Sarcoma/imunologia , Estruturas Linfoides Terciárias/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Células Dendríticas Foliculares/imunologia , Humanos , Mutação , Fenótipo , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Reprodutibilidade dos Testes , Sarcoma/classificação , Sarcoma/patologia , Taxa de Sobrevida , Microambiente Tumoral
10.
Anaesth Crit Care Pain Med ; 35(2): 87-92, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26592159

RESUMO

AIM: Over-triage rates related to the use of Vittel criteria are unknown. We compared severe stable trauma patients with and without significant visceral injuries. STUDY DESIGN: A single-centre retrospective analysis of a single-centre prospective cohort. PATIENTS AND METHODS: Trauma patients with at least one positive Vittel criterion from June 2010 to January 2012 in a level-1 trauma centre. Initial management included a systematic whole-body scanner. All significant lesions in stable trauma patients were recorded. RESULTS: A total of 252 trauma patients were admitted. One hundred and twenty were stable. In this group without vital distress, 72 (60%) had at least one occult lesion, 21 (17.5%) had an isolated orthopaedic injury and 27 (22.5%) had no injury. Thoracic injuries accounted for 44% of visceral injuries, abdominal for 17%, spinal for 16% and cerebral for 15%. Overall, the over-triage rate was 19%. Surgery for significant visceral injury was performed in 13 patients (18%) and arteriography in 4 patients (5.5%). Admission in an intensive care unit was required for 13 patients with occult injuries and for one patient without such a lesion (18% versus 2%, P=0.008). Hospital stays were longer in the group with visceral injuries (4±7 versus 9±8days; P=0.006). CONCLUSION: Vittel criteria use in trauma patients induces an acceptable over-triage rate. A large proportion of stable trauma patients have occult lesions. These visceral injuries frequently require special care. These data highlight the imperative need to transport major trauma patients immediately to a dedicated trauma centre and supports whole-body scanner use.


Assuntos
Triagem/normas , Ferimentos e Lesões/terapia , Adulto , Idoso , Angiografia , Cuidados Críticos , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Fechadas/diagnóstico por imagem , Fraturas Fechadas/cirurgia , Humanos , Longevidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos Torácicos/diagnóstico por imagem , Traumatismos Torácicos/terapia , Centros de Traumatologia , Imagem Corporal Total , Ferimentos e Lesões/diagnóstico por imagem , Ferimentos e Lesões/cirurgia
11.
Crit Care ; 17(1): R24, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23383619

RESUMO

INTRODUCTION: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection to identify patients at risk of multidrug-resistant (MDR) pathogens. The American Thoracic Society's recommendation for HCAP treatment is to use broad-spectrum and multiple antibiotics. However, this strategy may be economically expensive and promote antimicrobial resistance when a multisensitive pathogen is not identified. METHODS: We prospectively included all patients presenting with HCAP in the emergency department. Blood cultures and fiberoptic bronchoscope-guided distal protected small volume bronchoalveolar lavage (FODP mini-BAL) were performed in each patient. Empirical antibiotic therapy was adapted when microbiological findings were available. The primary objective was to assess whether FODP mini-BAL is more efficient than blood cultures in identifying pathogens with the ratio of identification between both techniques as principal criteria. RESULTS: We included 54 patients with HCAP. Pathogens were identified in 46.3% of cases using mini-BAL and in 11.1% of cases using blood cultures (P <0.01). When the patient did not receive antibiotic therapy before the procedure, pathogens were identified in 72.6% of cases using mini-BAL and in 9.5% of cases using blood cultures (P <0.01). We noted multidrug-resistant pathogens in 16% of cases. All bronchoscopic procedures could be performed in patients without complications. CONCLUSIONS: FODP mini-BAL was more efficient than blood cultures for identifying pathogens in patients presenting with HCAP. When bacteriological identification was obtained, antibiotic therapy was adapted in 100% of cases.See related letter by Sircar et al.,http://ccforum.com/content/17/2/428.


Assuntos
Lavagem Broncoalveolar/instrumentação , Lavagem Broncoalveolar/normas , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/terapia , Idoso , Idoso de 80 Anos ou mais , Lavagem Broncoalveolar/métodos , Broncoscopia/instrumentação , Broncoscopia/métodos , Broncoscopia/normas , Estudos de Coortes , Infecção Hospitalar , Feminino , Tecnologia de Fibra Óptica/instrumentação , Tecnologia de Fibra Óptica/métodos , Tecnologia de Fibra Óptica/normas , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/epidemiologia , Estudos Prospectivos
13.
Burns ; 39(5): 892-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23332161

RESUMO

Patients with face and neck burns (FNBs) often undergo prehospital intubation, or sustain inhalation injury which are risk factors for pneumonia in specific populations. Early onset pneumonia (EOP) might be caused by initial management. The primary goal of this study was to find risk factors for EOP in FNB patients. This is a retrospective, single-center trial. We screened all FNB patients for EOP with the Clinical Pulmonary Infection Score. Pneumonia diagnosis was with culture from a mini broncho-alveolar lavage. Potential risk factors for EOP were recorded. We included 152 patients, EOP was diagnosed in 58 (38.2%). EOP patients had a greater burned surface area median (20±17% vs. 10±17%; p<0.001), were more frequently intubated during prehospital care (65.5% vs. 21.3%; p<0.001), had more abnormal fiberoptic bronchoscopy at admission (58.6% vs. 19.1%; p=0.002) and a lower initial PaO2/FiO2 ratio (median 314±118.6 vs. 365±105.7; p=0.01). Multivariate analysis showed that only prehospital intubation was independently associated with EOP (odds ratio 3.6; 95% confidence interval, 1.34-10). Prehospital intubation appears to be an independent risk factor for EOP in severe burn patients. Assessments of the risk-benefit ratios of intubating and of not intubating those patients are indicated.


Assuntos
Queimaduras/complicações , Traumatismos Faciais/complicações , Lesões do Pescoço/complicações , Pneumonia/etiologia , Adulto , Idoso , Broncoscopia/estatística & dados numéricos , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
14.
Injury ; 43(5): 648-52, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-20843512

RESUMO

BACKGROUND: Hypothermia remains one of the major factors limiting surgery in extensively burned patients. We evaluated the effectiveness of an intravascular rewarming technique using CoolGard 3000™ system and Icy™ catheter to maintain normothermia during surgeries of severe burned patients and compared these findings to a historical control group. METHODS: This was a controlled non-randomised trial conducted between March 2008 and August 2009. Patients with burns greater than or equal to 40% of the total body surface area were included. Before the first burn excision, the Icy™ catheter was placed in the inferior vena cava via the femoral vein. Warming was then initiated and maintained until the bladder temperature reached over 37.5°C. The bladder temperature was recorded every 30min during surgery and for the first hour post-operatively and compared to a historical control group. RESULTS: We enrolled 4 patients and 11 surgeries in the CoolGard™ group and compared them to 3 patients and 10 surgeries in the historical cohort. All intraoperative bladder temperatures from T=30 were statistically different in the two groups. In the CoolGard™ group, no patient became hypothermic and no surgery was aborted because the patient's temperature had rapidly fallen below the threshold temperature (35.5°C). No device-related complication was reported. CONCLUSION: The use of an intravenous warming catheter is a novel approach to maintain normothermia during surgery in burn victims and may be more effective than traditional methods.


Assuntos
Queimaduras/complicações , Queimaduras/cirurgia , Hipotermia/terapia , Reaquecimento/métodos , Adulto , Temperatura Corporal/fisiologia , Procedimentos Endovasculares/métodos , Feminino , Humanos , Hipotermia/etiologia , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Período Pós-Operatório , Estudos Prospectivos , Bexiga Urinária
15.
Ann Pharmacother ; 45(2): e13, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21304040

RESUMO

OBJECTIVE: To describe a case of extensive intestinal necrosis with oral intake of calcium polystyrene sulfonate without sorbitol. CASE SUMMARY: A 73-year-old woman was admitted to the emergency department with abdominal pain. Abdominal computed tomography (CT) scan showed widespread dilatation of the bowel. The diagnosis of acute colonic pseudoobstruction was made. On day 3, her serum potassium level rose to 5.6 mEq/L. It was treated with hydrocortisone 100 mg/day and calcium polystyrene sulfonate 15 g/day via nasogastric tube from day 3 to day 6. On day 6, the severe abdominal pain recurred, with abdominal tenderness. CT scan showed pneumoperitoneum and peritoneal effusion. At surgery, 2 lenticular jejunal perforations and an ischemic cecum were found. Microscopic findings indicated that the transmural abscess contained massive inflammatory infiltrate and the cecal mucosa showed ulceration and inflammation with a fibrinous and purulent coating. Small gray-purple or blue angulated crystals were embedded in the cecal and most of the jejunal mucosal ulcers. On day 19, the patient died of multiple organ failure after her third laparotomy. DISCUSSION: Ion-exchanging resins are given orally or by retention enema for the treatment of hyperkalemia. The most commonly used and best-established resin is sodium polystyrene sulfonate. However, it is known to promote colonic necrosis when sorbitol is also given or especially in patients with renal failure or postoperative ileus. Calcium polystyrene sulfonate is another ion-exchange resin. There are few reports of adverse effects in the literature. Our case is interesting for 2 reasons: the resin given was calcium polystyrene sulfonate and sorbitol was not used. CONCLUSIONS: Like sodium polystyrene sulfonate, calcium polystyrene sulfonate is an ion-exchanging resin that can promote bowel necrosis. We believe that it should not be used with sorbitol or when bowel transit time is slowed.


Assuntos
Poliestirenos/efeitos adversos , Idoso , Ceco/irrigação sanguínea , Ceco/patologia , Pseudo-Obstrução do Colo/complicações , Pseudo-Obstrução do Colo/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Hiperpotassemia/complicações , Hiperpotassemia/tratamento farmacológico , Mucosa Intestinal/patologia , Perfuração Intestinal/induzido quimicamente , Intubação Gastrointestinal , Isquemia/induzido quimicamente , Jejuno/patologia , Necrose/induzido quimicamente , Sorbitol
16.
Cases J ; 1(1): 259, 2008 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-18945364

RESUMO

BACKGROUND: Tracheal rupture is a rare but life-threatening complication that most commonly occurrs after blunt trauma to the chest, but which may also complicate tracheal intubation. We report a case of post-intubation tracheal rupture after cataract surgery under general anesthesia treated conservatively. CASE PRESENTATION: Four hours after extubation, a 67 year-old woman developed subcutaneous emphysema of the facial, bilateral laterocervical and upper anterior chest. Tracheobronchial fiberendoscopy showed a posterior tracheal transmural rupture 4 cm long located 2.5 cm above the carina that opened in inspiration. The location of the lesion and features of the patient favoured conservative treatment with antibiotic cover. The patient made a full and uncomplicated recovery and was discharged fourteen days after the original injury. CONCLUSION: Two therapeutic strategies are currently employed for post-intubation tracheal rupture: a non-surgical strategy for small injuries and a surgical strategy for larger injuries. This case report presented the non-surgical therapeutic strategy of a large tracheal injury.

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