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PURPOSE OF THE STUDY: The critical shoulder angle (CSA) is formed by the combination of glenoid inclination and acromial index and has been shown related to rotator cuff tears and glenohumeral osteoarthritis. SLAP lesions today have an important place among bicipitolabral pathologies that cause intensive shoulder pain. We aimed to investigate the relationship between CSA and glenoid depth and SLAP lesions. MATERIAL AND METHODS: Between March 2017 and January 2022, 279 consecutive shoulder arthroscopy patients' MRI images were retrospectively examined. After the exclusion criteria, 191 patients were eligible. Patients with SLAP lesions (n=37) were assembled as the study group (Group 1), and patients with intact superior labrum (n=154) were named as the control group (Group 2). Critical shoulder angle (CSA) and glenoid depth measurements were performed using the preoperative MRI images. RESULTS: A total of 191 patients, of whom 84 were male (44%) were included. The mean age was 49.9±14.96 (range 18-79). There was a statistically signifi cant difference between the SLAP group (Group 1) and the control group (Group 2) in terms of CSA (p=0.032). The mean CSA was 31.66°±3.51° in Group 1 and 33.57° ±5.01° in Group 2. The cut-off value for CSA in patients with SLAP lesions was calculated as 32.85° and the area under the curve was 0.61, therefore a satisfactory association was observed between the groups. The mean glenoid depth was 4.32 ±1.25 mm in Group 1, and 4.39 ±0.32 mm in Group 2. There was no statistically signifi cant difference between the groups in terms of glenoid depth (p=0.136) and also no association between the glenoid depth and SLAP lesions was observed (cut-off=4.45 mm, AUC=0.32). CONCLUSIONS: Low CSA is associated with SLAP lesions, just as in glenohumeral osteoarthritis. Further prospective clinical studies are needed to enlighten the predisposing effect of CSA to SLAP lesions and the success of superior labral repairs. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.
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Osteoartrite , Ombro , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Escápula , Acrômio , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgiaRESUMO
OBJECTIVES: Matching treatment intensity to tumor biology is critical to precision oncology for head and neck squamous cell carcinoma (HNSCC) patients. We sought to identify biological features of tumor cell multinucleation, previously shown by us to correlate with survival in oropharyngeal (OP) SCC using a machine learning approach. MATERIALS AND METHODS: Hematoxylin and eosin images from an institutional OPSCC cohort formed the training set (DTr). TCGA HNSCC patients (oral cavity, oropharynx and larynx/hypopharynx) formed the validation set (DV). Deep learning models were trained in DTr to calculate a multinucleation index (MuNI) score. Gene set enrichment analysis (GSEA) was then used to explore correlations between MuNI and tumor biology. RESULTS: MuNI correlated with overall survival. A multivariable nomogram that included MuNI, age, race, sex, T/N stage, and smoking status yielded a C-index of 0.65, and MuNI was prognostic of overall survival (2.25, 1.07-4.71, 0.03), independent of the other variables. High MuNI scores correlated with depletion of effector immunocyte subsets across all HNSCC sites independent of HPV and TP53 mutational status although the correlations were strongest in wild-type TP53 tumors potentially due to aberrant mitotic events and activation of DNA-repair mechanisms. CONCLUSION: MuNI is associated with survival in HNSCC across subsites. This may be driven by an association between high levels of multinucleation and a suppressive (potentially exhausted) tumor immune microenvironment. Mechanistic studies examining the link between multinucleation and tumor immunity will be required to characterize biological drivers of multinucleation and their impact on treatment response and outcomes.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Medicina de Precisão , Prognóstico , Microambiente TumoralRESUMO
Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.
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Background: Although anthrax is a rare zoonotic infection, it still causes significant mortality and morbidity. In this multicenter study, which is the largest anthrax case series ever reported, we aimed to describe the factors leading to dissemination of cutaneous anthrax. Methods: Adult patients with cutaneous anthrax from 16 referral centers were pooled. The study had a retrospective design, and included patients treated between January 1, 1990 and December 1, 2019. Probable, and confirmed cases based upon CDC anthrax 2018 case definition were included in the study. A descriptive statistical analysis was performed for all variables. Results: A total of 141 cutaneous anthrax patients were included. Of these, 105 (74%) patients had probable and 36 (26%) had confirmed diagnosis. Anthrax meningitis and bacteremia occurred in three and six patients, respectively. Sequelae were observed in three patients: cicatricial ectropion followed by ocular anthrax (n = 2) and movement restriction on the left hand after surgical intervention (n = 1). One patient had gastrointestinal anthrax. The parameters related to poor outcome (p < 0.05) were fever, anorexia, hypoxia, malaise/fatigue, cellulitis, fasciitis, lymphadenopathy, leukocytosis, high CRP and creatinine levels, longer duration of antimicrobial therapy, and combined therapy. The last two were seemingly the consequences of dissemination rather than being the reasons. The fatality rate was 1.4%. Conclusions: Rapid identification of anthrax is crucial for prompt and effective treatment. Systemic symptoms, disseminated local infection, and high inflammatory markers should alert the treating physicians for the dissemination of the disease.
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BACKGROUND: Understanding biological differences between different racial groups of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies. METHODS: This study evaluated whether there were morphologic differences between HPV-associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis-derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin-eosin images and previously has been prognostic in HPV-associated OPSCC patients. In this study, the authors specifically evaluated whether the same MuNI cutoff that was prognostic of overall survival (OS) and disease-free survival in their previous study, TTR , is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, TB for Blacks and TW for Whites, for risk stratification. RESULTS: MuNI was statistically significantly different between Black (mean, 3.88e-4; median, 3.67e-04) and White patients (mean, 3.36e-04; median, 2.99e-04), with p = .0078. Using TTR , MuNI was prognostic of OS in the entire population with hazard ratio (HR) of 1.71 (p = .002; 95% confidence interval [CI], 1.21-2.43) and in White patients with HR of 1.72 (p = .005; 95% CI, 1.18-2.51). Population-specific cutoff, TW , yielded improved HR of 1.77 (p = .003; 95% CI, 1.21-2.58) for White patients, whereas TB did not improve risk-stratification in Black patients with HR of 0.6 (p = .3; HR, 0.6; 95% CI, 0.2-1.80). CONCLUSIONS: Histological difference between White and Black patient tumors in terms of multinucleated tumor cells suggests the need for considering population-specific prognostic biomarkers for personalized risk stratification strategies for HPV-associated OPSCC patients.
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Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Biomarcadores , Carcinoma de Células Escamosas/patologia , Amarelo de Eosina-(YS) , Neoplasias de Cabeça e Pescoço/complicações , Hematoxilina , Humanos , Papillomaviridae , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicaçõesRESUMO
OBJECTIVE: Tissue slides from Oral cavity squamous cell carcinoma (OC-SCC), particularly the epithelial regions, hold morphologic features that are both diagnostic and prognostic. Yet, previously developed approaches for automated epithelium segmentation in OC-SCC have not been independently tested in a multi-center setting. In this study, we aimed to investigate the effectiveness and applicability of a convolutional neural network (CNN) model to perform epithelial segmentation using digitized H&E-stained diagnostic slides from OC-SCC patients in a multi-center setting. METHODS: A CNN model was developed to segment the epithelial regions of digitized slides (n = 810), retrospectively collected from five different centers. Deep learning models were trained and validated using well-annotated tissue microarray (TMA) images (n = 212) at various magnifications. The best performing model was locked down and used for independent testing with a total of 478 whole-slide images (WSIs). Manually annotated epithelial regions were used as the reference standard for evaluation. We also compared the model generated results with IHC-stained epithelium (n = 120) as the reference. RESULTS: The locked-down CNN model trained on the TMA image training cohorts with 10x magnification achieved the best segmentation performance. The locked-down model performed consistently and yielded Pixel Accuracy, Recall Rate, Precision Rate, and Dice Coefficient that ranged from 95.8% to 96.6%, 79.1% to 93.8%, 85.7% to 89.3%, and 82.3% to 89.0%, respectively for the three independent testing WSI cohorts. CONCLUSION: The automated model achieved a consistently accurate performance for automated epithelial region segmentation compared to manual annotations. This model could be integrated into a computer-aided diagnosis or prognosis system.
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Carcinoma de Células Escamosas , Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: COVID-19 pandemic spread around the world like an infectious disease that presents waved effects on patients. Some patients needed ICU and respiratory support. Some patients only had flu-like symptoms. Cytokine storm and elevated ROS were serious problems for treatment. Apoptotic genes and CYP Family are part of these mechanisms. AIM: In this study, our aim was to examine the gene expression CYP2E1 and Caspase-3 in patients with COVID-19 infection. METHOD: 60 COVID-19(+) patients (ICU and non-ICU patients) and 30 healthy volunteers were enrolled to study. To measure the level of gene expression qPCR was used. The 2-ΔΔCt method was utilized to analyze gene expression. RESULTS: The expression of CYP2E1 and Caspase-3 genes showed a significant discrepancy between patients and healthy individuals. Caspase-3 expression increased (p=0,0041) but CYP2E1 expression decreased (p=0,0214) in COVID-19 patients compared to healthy individuals. Both levels of gene expression were lower in patients with affected lungs than patients with unaffected lungs (p<0,05). Laboratory findings including d-Dimer, LDH, platelet count, lymphocyte count were related to both gene expressions (p<0,05). We found no correlation between CYP2E1 and Caspase-3 expressions. CONCLUSION: The expression of Caspase-3 demonstrated apoptotic situations of patients but was not related to the CYP2E1 expression level. CYP2E1 gene expression is an important actor to metabolize endogens and xenobiotics however, COVID-19 patients demonstrated decreased CYP2E1 expression. CYP2E1 and Caspase-3 gene expression levels may be used as a diagnostic tool for COVID-19 patients.
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Membrane antigens are phenotypic signatures of cells used for distinguishing various subpopulations and, therefore, are of great interest for diagnosis of diseases and monitoring of patients in hematology and oncology. Existing methods to measure antigen expression of a target subpopulation in blood samples require labor-intensive lysis of contaminating cells and subsequent analysis with complex and bulky instruments in specialized laboratories. To address this long-standing limitation in clinical cytometry, we introduce a microchip-based technique that can directly measure surface expression of target cells in hematological samples. Our microchip isolates an immunomagnetically-labeled target cell population from the contaminating background in whole blood and then utilizes the differential responses of target cells to on-chip magnetic manipulation to estimate their antigen expression. Moreover, manipulating cells with chip-sized permanent magnets and performing quantitative measurements via an on-chip electrical sensor network allows the assay to be performed in a portable platform with no reliance on laboratory infrastructure. Using our technique, we could successfully measure expressions of the CD45 antigen that is commonly expressed by white blood cells, as well as CD34 that is expressed by scarce hematopoietic progenitor cells, which constitutes only â¼0.0001% of all blood cells, directly from whole blood. With our technology, flow cytometry can potentially become a rapid bedside or at-home testing method that is available around the clock in environments where this invaluable assay with proven clinical utility is currently either outsourced or not even accessible.
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Antígenos , Células-Tronco Hematopoéticas , Antígenos CD34/análise , Eletrônica , Citometria de Fluxo/métodos , Células-Tronco Hematopoéticas/química , HumanosRESUMO
BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.
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Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Processamento de Imagem Assistida por Computador , Carcinoma de Células Escamosas de Cabeça e Pescoço , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de SobrevidaRESUMO
Antimicrobial photodynamic therapy (aPDT) and antimicrobial photothermal therapy (aPTT) are promising local and effective alternative therapies for antibiotic resistant bacterial infections and biofilms. A combination of nanoparticles and organic photosensitizers offers a great opportunity to combine PDT and PTT for effective eradication of both planktonic bacteria and their biofilms. In this work, photo-induced antibacterial activity of indocyanine green (ICG), 3-aminopropylsilane coated superparamagnetic iron oxide nanoparticles (APTMS@SPIONs) and ICG loaded APTMS@SPIONs was evaluated on planktonic cells and biofilms of Gram-negative (E. coli, K. pneumoniae, P. aeruginosa) and Gram-positive (S. epidermis) bacteria. A relatively low dose of ICG (25 µg mL-1) and SPIONs (0.425 µg mL-1 nanoparticle) in combination with single, short (10 min) laser irradiation at 808 nm with a power of 1150 mW was used in this study. No dark toxicity of the agents or antibacterial effect of the laser irradiation was observed. The charge of the particles did not provide a significant difference in their penetration to Gram-negative versus Gram-positive bacterial strains or their biofilms. APTMS@SPION/laser treatment completely eliminated P. aeruginosa and provided 7-log reduction in the colony forming unit (CFU) of E. Coli, but was not effective on the other two bacteria. This is the first example for antibacterial phototoxicity of this nanoparticle. ICG/laser and ICG-APTMS@SPION/laser treatments provided complete killing of all planktonic cells. Successful eradication of all biofilms was achieved with ICG/laser (3.2-3.7 log reduction in CFUs) or ICG-APTMS@SPION/laser treatment (3.3-4.4 log reduction in CFUs). However, an exceptionally high, 6.5-log reduction as well as a dramatic difference between ICG versus ICG/APTMS@SPION treatment was observed in K. pneumoniae biofilms with ICG-APTMS@SPION/laser treatment. Investigation of the ROS production and increase in the local temperature of the biofilms that were subjected to phototherapy suggested a combination of aPTT and aPDT mechanisms for phototoxicity, exhibiting a synergistic effect when ICG-APTMS@SPION/laser was used. This approach opens an exciting and novel avenue in the fight against drug resistant infections by successfully utilizing the antimicrobial and antibiofilm activity of low dose FDA approved optically traceable ICG and relatively low cost clinically acceptable iron oxide nanoparticles to enable effective aPDT/aPTT combination, induced via short-duration laser irradiation at a near-infrared wavelength.
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Verde de Indocianina , Fotoquimioterapia , Antibacterianos/farmacologia , Escherichia coli , Lasers Semicondutores , Nanopartículas Magnéticas de Óxido de Ferro , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Terapia FototérmicaRESUMO
El trombo tumoral es una extensión de tumor maligno intravascular que puede ocurrir en varios tipos de cáncer. Los carcinomas hepatocelulares (CHC) son causas comunes de trombo maligno. La presencia de un trombo maligno debido al CHC tiene un pronóstico sombrío, que afecta las opciones de tratamiento. Presentamos 3 casos de trombos tumorales debidos a CHC avanzado detectado por 18F-FDG PET/TC
Tumor thrombus is an intravascular malign tumor extension that may occur in various types of cancer. Hepatocellular carcinomas (HCC) are common causes of malign thrombus. The presence of a malign thrombus due to HCC has a dismal prognosis, which affects treatment choices. We present three cases of tumor thrombi due to advanced HCC detected by 18F-FDG PET/CT
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Humanos , Masculino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Trombose/diagnóstico por imagem , Carcinoma Hepatocelular/complicações , Fluordesoxiglucose F18/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Transplante de FígadoRESUMO
Tumor thrombus is an intravascular malign tumor extension that may occur in various types of cancer. Hepatocellular carcinomas (HCC) are common causes of malign thrombus. The presence of a malign thrombus due to HCC has a dismal prognosis, which affects treatment choices. We present three cases of tumor thrombi due to advanced HCC detected by 18F-FDG PET/CT.
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Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/secundário , Fluordesoxiglucose F18 , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodosRESUMO
INTRODUCTION: Medical and surgical treatment options are available for patients with diabetic foot ulcers. In more severe cases, amputation decisions are determined by patient comorbidities, performance, imaging studies, and clinical examination results. However, an objective indicator that predicts how this amputation process will end has not yet been clarified. This study identifiies clinical characteristics that can be predictors of the need for diabetic foot amputation among patients. METHODS: In this retrospective observational study, a total of 400 patients with type 2 diabetes who were over the age of 18 and possessed diabetic foot ulcers were examined. The clinical, radiological, and scintigraphic profiles of these patients including age, gender, duration of diabetes, smoking history, previous diabetic foot amputation, presence of hypertension (HT), coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease, cardiovascular disease, retinopathy, neuropathy and nephropathy were analyzed. RESULTS: Of the 400 patients with diabetic foot ulcers, 143 (35.75%) underwent foot amputation. Moreover, the frequency of proteinuria in amputees was significantly higher than in non-amputees (p<0,05). Amputees also exhibited significantly longer smoking histories (p<0,001), and the frequency of reamputation was significantly higher in those who possesed histories of previous amputation (p=0.038). After multivariate analysis PAD presence and previous diabetic ulcer history were the significant factors to determine the amputation decision. CONCLUSION: The following patient characteristics were determined as being effective for predicting the need for amputation: male sex, CAD, PAD, HT, proteinuria, ulcers with Wagner Stages 4-5, smoking histories, previous diabetic ulcer histories, and previous amputation histories. The specificity of the model with these variables was determined as 86% in the patients who did not need amputation. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history. Still, further and more extensive research with higher numbers of patients is necessary for determining more precisely the need for amputation.
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Amputação Cirúrgica , Diabetes Mellitus Tipo 2/epidemiologia , Pé Diabético/cirurgia , Amputação Cirúrgica/efeitos adversos , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Pé Diabético/diagnóstico , Pé Diabético/epidemiologia , Humanos , Hipertensão/epidemiologia , Seleção de Pacientes , Doença Arterial Periférica/epidemiologia , Proteinúria/epidemiologia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic ß cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients' own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward âthe implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.
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Escherichia coli ST131 is a cause for global concern because of its high multidrug resistance and several virulence factors. In this study, the contribution of acrAB-TolC efflux system of E. coli ST131 to fluoroquinolone resistance was evaluated. A total of nonrepetitive 111 ciprofloxacin-resistant E. coli isolates were included in the study. Multilocus sequence typing was used for genotyping. Expressions of acrA, acrB, and TolC efflux pump genes were measured by RT-PCR. Mutations in marA, gyrA, parC, and aac(6')-lb-cr positivity were studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified as ST131, and 52 (81.3%) of the ST131 isolates belonged to H30-Rx subclone. In ST131, CTX-M 15 positivity (73%) and aac(6')-lb-cr carriage (75%) were significantly higher than those in non-ST131 (12.8% and 51%, respectively) (P < 0.05). The ampicillin-sulbactam (83%) resistance was higher, and gentamicin resistance (20%) was lower in ST131 than that in non-ST131 (64% and 55%, respectively) (P = 0.001 and P = 0.0002). Numbers of the isolates with MDR or XDR profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded in all quinolone-resistant isolates. However, marA gene was more overexpressed in ST131 compared to that in non-ST131 (median 5.98 vs. 3.99; P = 0.0007). Belonging to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate with efflux pump expressions. In conclusion, the marA regulatory gene of AcrAB-TolC efflux pump system has a significant impact on quinolone resistance and progression to MDR profile in ST131 clone. Efflux pump inhibitors might be alternative drugs for the treatment of infections caused by E. coli ST131 if used synergistically in combination with antibiotics.
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Proteínas de Transporte/genética , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Quinolonas/farmacologia , Antibacterianos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana/métodos , Tipagem de Sequências Multilocus/métodos , Fatores de Virulência/genéticaRESUMO
This article describes the emergence of resistance and predictors of fatality for 1556 cases of healthcare-associated Gram-negative bloodstream infection in 2014 and 2015. The colistin resistance rate in Klebsiella pneumoniae was 16.1%, compared with 6% in 2013. In total, 660 (42.4%) cases were fatal. The highest fatality rate was among patients with Acinetobacter baumannii bacteraemia (58%), followed by Pseudomonas aeruginosa (45%), Klebsiella pneumoniae (41%), Enterobacter cloacae (32%) and Escherichia coli (28%). On multi-variate analysis, the minimum inhibitory concentrations for carbapenems [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.04; P = 0.002] and colistin (OR 1.1, 95% CI 1.03-1.17; P = 0.001) were found to be significantly associated with fatality.
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Antibacterianos/farmacologia , Bacteriemia/mortalidade , Colistina/farmacologia , Infecção Hospitalar/mortalidade , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Carbapenêmicos/farmacologia , Infecção Hospitalar/microbiologia , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Based on public opinion surveys, although 75% of people state that they would donate the organs of one of their relatives, in reality, the rate of the people who donate the organs of their relatives is 24%. To decrease the organ shortage, the key point is to understand the difference between intention and real behavior. For this reason, in this study, analyses of variables related to the potential organ donor families' decisions of approval or refusal for organ harvesting were analyzed. The interviews were conducted with 101 families who made a decision about organ donation between 2010 and 2014. The variables, strongly related with the family decision, are the wishes of the deceased persons about donation, suspicions regarding brain death, the desire to protect body integrity, and the satisfaction levels of the families with the approaches of medical personnel. The findings, obtained from qualitative data, also support the quantitative data. The results indicate that both education of the public about maintaining a positive attitude toward organ donation and education of health professionals can be key factors in decreasing the organ shortage.
Assuntos
Atitude Frente a Saúde , Tomada de Decisões , Família , Obtenção de Tecidos e Órgãos , Adulto , Morte Encefálica , Família/psicologia , Feminino , Humanos , Masculino , Opinião Pública , Inquéritos e Questionários , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , TurquiaRESUMO
This article describes the prevalence of antibiotic resistance and predictors of mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN-BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was 6%. Multi-variate analysis showed that age >70 years [odds ratio (OR) 2, 95% confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI 1.09-4.07), ventilator-associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07-1.13) were significantly associated with mortality.
Assuntos
Bacteriemia/mortalidade , Infecção Hospitalar/mortalidade , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/mortalidade , Adulto , Idoso , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Bactérias Gram-Negativas/classificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Turquia/epidemiologiaRESUMO
OBJECTIVE: Anatomical variations of the extrahepatic biliary tree are frequently seen and may cause challenging conditions for surgeons. We aimed to investigate the morphological variations of the gallbladder in patients who underwent cholecystectomy and their effects during and after the surgery, by using a new anatomical classification. PATIENTS AND METHODS: Dissection time, perioperative bleeding, perioperative/postoperative complication rates, the difference between preoperative/postoperative hematocrit and leukocyte levels of 164 symptomatic cholelithiasis patients who underwent laparoscopic cholecystectomy were evaluated. The patients' gallbladders were categorized in "seven" different types regarding their anatomical positions and morphometric relations with the liver's acute margin and fossa of the gallbladder. Relations between these gallbladders types and perioperative/postoperative parameters were also examined. RESULTS: The median time to complete the dissection of the gallbladder from the fossa was 375.5 seconds. The mean length of the fossa was 68.06 ± 15.08 mm, the average size of the gallbladder was 92.10 ± 18.79 mm. A positive correlation was found between dissection time and length of fossa vesica and also in the size of the gallbladder (p = 0.003, p = 0.034). Moreover, a positive correlation was found between the dissection time and the perioperative perforation risk of the gallbladder (p = 0.005). The most common type of gallbladder was type I and III (23.2%). The least common gallbladder type among the patients assessed as part of the study was type VI (6.7%). When the gallbladder types were compared, the perioperative perforation rate of the gallbladder wall was found to be significantly higher in morphological type V (p = 0.014). CONCLUSIONS: The perioperative perforation rate of the gallbladder wall was found significantly higher in morphological type V. To perform a safe cholecystectomy, surgeons should be aware of anatomical variations of the gallbladder and its relations with the liver parenchyma, which are important for surgical strategies.