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Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract whose etiology is unknown, which can transmurally affect any segment of the intestine and/or the perineal region. Worldwide, the incidence of inflammatory bowel disease has increased in recent decades, and the same upward trend can be seen in South America. At national level, there are no official data, however, the increase in the number of publications in the last 20 years confirms this upward trend. Crohn's disease is a forgotten disease and does not have implemented clinical guidelines based on evidence that contribute to clinicians in decision making. In this sense, the Peruvian Association for the Study of the Intestine considers the preparation of this document relevant and timely. clinical contextualized for Peru.
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Doença de Crohn , Humanos , Doença de Crohn/terapia , Doença de Crohn/diagnóstico , PeruRESUMO
This paper presents and demonstrates the three logic processing levels based on complementary photonic crystal logic devices through photonic integrated circuit modeling. We accomplished a set of logic circuits including AND, OR, NAND, NOR, XOR, FAN-OUT, HALF ADDER, and FULL ADDER based on photonic crystal slab platforms. Furthermore, we achieved efficient all-optical logic circuits with contrast ratios as high as 5.5 dB, demonstrated in our simulation results, guaranteeing well-defined output power values for logic representations; a clock-rate up to 2 GHz; and an operating wavelength at λ ≈ 1550 nm. Thus, we can now switch up for high computing abstraction levels to build photonic integrated circuits rather than isolated gates or devices.
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We theoretically propose and demonstrate through numerous simulations complementary photonic crystal integrated logic (CPCL) devices. Simulation results provide demonstration of a highly efficient clock rate, higher than 20 GHz, guaranteeing operation at both input and output with the same wavelength (around λ=1550nm). The proposed devices show well-defined output power values representing the two logic states 1 and 0, with a contrast ratio as high as 6 dB. The results presented here provide countless possibilities for future research, targeting the development of photonic crystal logic and communications systems with CPCLs acting as the core hardware devices.
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Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, primary cutaneous CD30 lymphoproliferative disorders (pc CD30 LPD) being the second most prevalent. There is evidence that MF and pc CD30 LPD may coexist and share T-cell clonality, suggesting a common origin. These findings were supported by a T-cell receptor clonality assessment by the polymerase chain reaction coupled with capillary electrophoresis, although results produced by this method may be ambiguous. We describe an otherwise healthy 46-year-old man who developed, over the course of 5 months, a tumor consisting of primary cutaneous anaplastic large cell lymphoma and, subsequently, several papules of lymphomatoid papulosis (LyP). Both lymphomas appeared on a single patch of MF, which had been present on the patient's right buttock for at least 2 years. T-cell receptor clonality of the 3 types of neoplastic lesions and apparently non-involved skin were assessed by a next-generation sequencing-based method. We found that MF, primary cutaneous anaplastic large cell lymphoma and LyP harbored the same top 2 clones. Non-involved skin harbored other T-cell clones. In this patient, these findings suggest that MF, LyP and pc CD30 LPD were different clinicopathological manifestations arising from the neoplastic proliferation of the same T-cell clone.
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Linfoma Anaplásico de Células Grandes/patologia , Papulose Linfomatoide/patologia , Micose Fungoide/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/patologia , Humanos , Antígeno Ki-1 , Masculino , Pessoa de Meia-Idade , Linfócitos T/patologiaRESUMO
A new crosslinking formulation using gelatin (G) and cactus mucilage (CM) biopolymers was developed, physicochemically characterized and proposed as an alternative wall material to traditional gelatin capsules (softgels). The effect of G concentration at different G/CM ratios (3:1, 1:1 and 1:3) was analyzed. Transparency, moisture content (MC), solubility in water (SW), morphology (scanning electron microscopy, SEM), vibrational characterization (Fourier transform infrared, FTIR), color parameters (CIELab) and thermal (differential scanning calorimetry/thermogravimetric analysis, DSC/TGA) properties of the prepared composite (CMC) capsules were estimated and compared with control (CC) capsules containing only G and glycerol. In addition, the dietary fiber (DF) content was also evaluated. Our results showed that the transparency of composite samples decreased gradually with the presence of CM, the G/CM ratio of 3:1 being suitable to form the softgels. The addition of CM decreased the MC, the SW and the lightness of the capsules. Furthermore, the presence of polysaccharide had significant effects on the morphology and thermal behavior of CMC in contrast to CC. FTIR spectra confirmed the CMC formation by crosslinking between CM and G biopolymers. The addition of CM to the softgels formulation influenced the DF content. Our findings support the feasibility of developing softgels using a formulation of CM and G as wall material with nutritional properties.
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Fibras na Dieta , Gelatina/química , Opuntia/química , Polissacarídeos/química , CápsulasRESUMO
The histiocytoses are rare disorders characterized by the accumulation of macrophage, dendritic cell, or monocyte-derived cells in various tissues and organs of children and adults. More than 100 different subtypes have been described, with a wide range of clinical manifestations, presentations, and histologies. Since the first classification in 1987, a number of new findings regarding the cellular origins, molecular pathology, and clinical features of histiocytic disorders have been identified. We propose herein a revision of the classification of histiocytoses based on histology, phenotype, molecular alterations, and clinical and imaging characteristics. This revised classification system consists of 5 groups of diseases: (1) Langerhans-related, (2) cutaneous and mucocutaneous, and (3) malignant histiocytoses as well as (4) Rosai-Dorfman disease and (5) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Herein, we provide guidelines and recommendations for diagnoses of these disorders.
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Células Dendríticas , Transtornos Histiocíticos Malignos , Histiocitose de Células de Langerhans , Histiocitose de Células não Langerhans , Macrófagos , Adulto , Células Dendríticas/classificação , Células Dendríticas/patologia , Feminino , Transtornos Histiocíticos Malignos/classificação , Transtornos Histiocíticos Malignos/patologia , Histiocitose de Células de Langerhans/classificação , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células não Langerhans/classificação , Histiocitose de Células não Langerhans/patologia , Humanos , Macrófagos/classificação , Macrófagos/patologia , MasculinoRESUMO
A female infant presented with an ulcerated lesion on the right side of the vulva. Histopathology showed a suprabasal acantholytic blister with intact papillae protruding into the blister cavity and a few dyskeratotic cells. There were no signs of injury on other locations. Family history was unremarkable. Our patient may have linear Hailey-Hailey disease of the vulva, most likely a case of type 1 mosaic.
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Pênfigo Familiar Benigno/diagnóstico , Doenças da Vulva/patologia , Acantólise/patologia , Feminino , Humanos , Lactente , Mosaicismo , Vulva/patologiaRESUMO
BACKGROUND: endoscopic dilation is considered as the treatment of choice for esophageal strictures. However, there are no studies in our region that have assessed the safety of the procedure. OBJECTIVE: to assess the safety of esophageal dilation and the factors associated with the development of complications. MATERIALS AND METHODS: a retrospective cohort was studied. All patients referred for esophageal dilation between January 2015 and June 2017 were included in the study. A complication rate was obtained and the association between nonadherence to the "rule of 3" and the development of complications was determined. Other predictive factors associated with complication development were also analyzed. RESULTS: a total of 164 patients that underwent 474 dilations were included in the study. Surgical anastomosis stricture was the most prevalent etiology. A total of six complications occurred, including three perforations (0.63%), two bleeding events (0.42%) and one episode of significant pain that required post-procedure observation (0.21%). Endoscopic esophageal dilation without adherence to the "rule of 3" was not associated with a higher risk of complications. Balloon dilation was the only predictive factor for complications. CONCLUSIONS: esophageal dilation is a safe procedure. Nonadherence to the "rule of 3" does not appear to be associated with a higher risk of complications, including esophageal perforation.
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Dilatação/efeitos adversos , Estenose Esofágica/cirurgia , Esofagoscopia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Perfuração Esofágica/etiologia , Esofagoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To provide evidence-based clinical recommendations for the evaluation and management of patients with upper gastrointestinal bleeding (UGB) in the Peruvian Social Security (EsSalud). MATERIALS AND METHODS: A local guideline development group (local GDG) was established, including specialists in gastroenterology and methodologists. The local GDG formulated 11 clinical questions to be answered by this clinical practice guide (CPG). We searched and selected CPG of UGB published from 2012, which answered the posed questions and obtained a score higher than 60% in domains 1 and 3 of the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. During September 2017, bibliographic searches were conducted in Pubmed, to update 9 clinical questions of the preselected CPGs, and to answer 2 de novo questions. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG reviewed the evidence and formulated the recommendations, points of good clinical practice and the flowchart of evaluation and management, using the GRADE methodology Lastly, the CPG was approved with Resolución N° 80-IETSI-ESSALUD-2017. RESULTS: This CPG addressed 11 clinical questions, divided into four themes: risk assessment, initial management, management of non-variceal UGB, and management of variceal UGB. Based on these questions, 10 recommendations (7 strong recommendations and 3 weak recommendations), 24 points of good clinical practice, and 2 flow charts were formulated. CONCLUSION: This article is the summary of the EsSalud' CPG, where the available scientific evidence on evaluation and management of UGB was evaluated.
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Hemorragia Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Programas Nacionais de Saúde , Peru , Previdência SocialRESUMO
BACKGROUND: Paravalvular aortic regurgitation after transcatheter aortic valve implantation is associated with a hemodynamic deterioration and a poor outcome. We aim to determine the early hemodynamic effect of paravalvular aortic regurgitation in relation with the change in the left ventricle filling pattern and to assess their clinical outcome. MATERIAL AND METHODS: Eighty-two consecutive patients referred for transcatheter aortic valve implantation were included. Patients were classified according to the change in the left ventricular filling pattern, and significant paravalvular aortic regurgitation (grade ≥ 2) was reported. Follow-up and incidence of death and hospitalization for heart failure were reported. RESULTS: Sixteen patients (19·5%) presented a worsening of left ventricular filling pattern. The incidence of significant paravalvular aortic regurgitation was higher in the group with a worsening of left ventricular filling pattern (56·3% vs. 19·7%; P = 0·009). In the multivariate analysis, the only variable significantly associated with the worsening of left ventricular filling pattern was the significant paravalvular aortic regurgitation (OR 4·84; 95% CI 1·23 - 19·1; P = 0·024). During the follow-up (642·5 days), there was a higher incidence of the endpoint of death or hospitalization for heart failure in the group with a worsening of left ventricular filling pattern (62·5% vs. 31·8%; P = 0·042) and a lower event-free survival rate (long rank test = 0·013). CONCLUSIONS: The presence of a significant paravalvular aortic regurgitation is associated with a worsening in parameters of diastolic function. This finding should alert the cardiologist as patients with a worsening of left ventricular filling pattern present a higher incidence of paravalvular aortic regurgitation and a less favourable outcome.
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Insuficiência da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Disfunção Ventricular Esquerda/etiologia , Idoso , Idoso de 80 Anos ou mais , Insuficiência da Valva Aórtica/fisiopatologia , Progressão da Doença , Ecocardiografia/métodos , Feminino , Humanos , Masculino , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
PURPOSE: To assess the long-term impact of postoperative two-field-conventional radiotherapy (RT) on neurocognitive functions of adult patients with operated pituitary adenomas (PA). METHODS: We selected 124 adult patients with operated PA-56 of whom had also received RT-recorded their main clinical data and performed a neuropsychological assessment in all of them that included 15 standardized tests, and a cerebral SPECT in eight patients. Comparative analyses were carried out on major clinical and neurocognitive domains between irradiated and not irradiated patients, and on cerebral SPECT source. RESULTS: Compared with non-irradiated patients, irradiated patients performed significantly worse on Barcelona's story recall test (P < 0.001) and arithmetic problems (P < 0.03) and on five categories of the Wisconsin card sorting test, especially on perseverative answers and errors (P < 0.001) without differences in other examined functional domains. RT was the only factor associated with worse results in these tests regardless other clinical and treatment-related variables. Kaplan-Meier analysis suggested that the probability of achieving poorer results with time was related to RT total dose and field-size, type of PA and age at the time of RT. Four of the five SPECTS performed in irradiated patients revealed a similar altered perfusion in the left temporal lobe cortical region. CONCLUSIONS: In adult patients with operated PA, RT was independently associated with an impairment on verbal memory and executive function, when compared to non-irradiated patients. Our data suggest that diagnosis of acromegaly or Cushing's disease, and age at the time of RT were able to modulate this long-term radio-induced neurocognitive sequelae.
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Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/radioterapia , Radioterapia/efeitos adversos , Acromegalia/complicações , Adulto , Fatores Etários , Cognição/efeitos da radiação , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Hipersecreção Hipofisária de ACTH/complicações , Neoplasias Hipofisárias/cirurgiaRESUMO
AIMS: To assess the feasibility and reliability of aortic valve area (AVA) planimetry by means of three-dimensional transesophageal echocardiography (3DTEE) as compared with the transthoracic echocardiogram (TTE) calculation of AVA, to determine the systematic deviations between measurements, and to describe the distribution of mean systolic in relation with 3DTEE anatomical AVA. METHODS AND RESULTS: Three hundred seven patients with aortic valve stenosis (AVS) underwent both TTE and 3DTEE for AVA measurement by means of the continuity equation and direct anatomical planimetry, respectively. AVA planimetry was achieved in 282 (91.9%) of patients. Severity of the aortic valve calcification was independently associated with a poorer performance of planimetry. Intraclass correlation coefficient yielded a 0.848 (95% CI: 0.807-0.879) value. 3DTEE rendered a mild constant underestimation of AVA in comparison with TTE. Severe aortic stenosis according to the area criterion (<1 cm(2) ) despite mean systolic gradient below 40 mm Hg was detected in 37.6% of the study population, and in 33.7% of the subset of patients with preserved left ventricular ejection fraction. CONCLUSIONS: Reliability of AVA planimetry by 3DTEE in comparison with the calculation by TTE is good, but 3DTEE underestimates slightly the measurement. Feasibility of the technique is good but independently affected by valvular calcification. Inconsistent classification of AVS severity as graded by AVA or mean systolic gradient is observed in the overall population and in patients with preserved systolic function.
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Algoritmos , Estenose da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/métodos , Interpretação de Imagem Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc. METHODS: We prospectively enrolled 65 patients with SSc (age 54±14 years, 30% female) followed in CHU Sart-Tilman, Liège, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise. RESULTS: EIPH was present in 21 patients. During FU (27±18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63±14 vs 52±13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30±6 vs 24±6; P=0.007 and 57±13 vs 44±13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112±106 vs 26±19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ß=2.4±1.1; P=0.03), EIPH (ß=2.30±1.13; P=0.04), FUPH (ß=0.24±0.09; P=0.01 and ß=3.52±1.16; P=0.002, respectively;) and BNP (ß=0.08±0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001). CONCLUSION: Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc.
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Doenças Cardiovasculares/diagnóstico , Ecocardiografia sob Estresse , Microcirculação , Angioscopia Microscópica , Unhas/irrigação sanguínea , Peptídeo Natriurético Encefálico/sangue , Escleroderma Sistêmico/complicações , Adulto , Idoso , Pressão Arterial , Bélgica , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Medição de Risco , Fatores de Risco , Escleroderma Sistêmico/diagnósticoRESUMO
BACKGROUND: Interleukin (IL)-33 and sST2 are molecules with an opposite pathophysiologic implications in the myocardial response after acute myocardial infarction (AMI). Both may be a target for therapeutic interventions. The kinetics of IL-33 and sST2 expression in infarcted myocardium and their correlation with the ongoing processes of fibrosis, inflammation and apoptosis remains poorly defined. MATERIALS AND METHODS: Fifty Wistar rats underwent left anterior descending coronary artery surgical ligation and were sacrificed at 1, 2, 4, 12 or 24 weeks post-AMI. A sham-operated group was also included. The mRNA cardiac expression levels of IL-33, sST2, fibrosis markers, inflammatory markers and apoptosis markers were assessed by RT-PCR. The protein expression of IL-33 was also measured by Western blotting. RESULTS: The mRNA levels of IL-33 and sST2 were upregulated in the infarcted myocardium during the first week after AMI. However, while IL-33 levels remained elevated during the first 12 weeks post-AMI, sST2 levels showed a marked drop at 4 weeks. IL-33 protein expression showed a similar kinetic than mRNA expression. The expression of sST2 positively correlated with cardiac gene expression of inflammatory and fibrosis markers. However, the IL-33 level did not correlate with these cardiac remodelling markers. No correlation of sST2 with apoptosis markers was observed. CONCLUSION: After AMI, expression of sST2 is rapidly upregulated during the first 4 weeks and, in contrast to IL-33, its levels correlated with the ongoing processes of fibrosis and inflammation. These findings suggest differential regulation of IL33 and sST2. Therapeutic modulation of early sST2 expression may be of greater importance to prevent adverse remodelling after AMI.
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Insuficiência Cardíaca/metabolismo , Interleucinas/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/patologia , Receptores de Interleucina-1/metabolismo , Animais , Apoptose/fisiologia , Biomarcadores/metabolismo , Vasos Coronários/cirurgia , Fibrose/metabolismo , Fibrose/patologia , Interleucina-33 , Ligadura , Masculino , Infarto do Miocárdio/patologia , Miocardite/metabolismo , Miocardite/patologia , RNA Mensageiro/metabolismo , Ratos Wistar , Regulação para Cima , Remodelação Vascular/fisiologiaRESUMO
BACKGROUND: Despite the potential of corticosteroids in treating community-acquired pneumonia (CAP), conflicting evidence exists regarding their effect on mortality. To address this gap and provide new insights, we conducted a pre-specified subgroup meta-analysis of corticosteroid use in CAP patients, focusing on the ICU versus non-ICU subsets. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to May 2023 for randomized controlled trials (RCTs). The primary outcomes of interest were mortality, need for mechanical ventilation, need for ICU admission, and treatment failure. Secondary outcomes analysed were the need for hospital readmission, length of hospital stay, length of ICU stay, gastrointestinal (GI) bleeding, secondary infections, and hyperglycaemic events. The results were analysed through the random-effects model. A p-value < 0.05 was considered significant. RESULTS: Eighteen randomized controlled trials (n = 4472) analyzing patients withCAP were included. Our results suggest that corticosteroids significantly reduced the incidence of mortality (RR: 0.66; 95 % CI: 0.54, 0.81; P = <0.0001) and need for mechanical ventilation (RR: 0.57; 95 % CI: 0.44, 0.73; P = <0.00001). It was also observed that corticosteroids significantly decrease the lengths of ICU (MD: -1.67; 95 % CI: -2.97, -0.37; P = 0.01) and hospital stay (MD: -1.94; 95 % CI: -2.89, -0.98; P = 0.0001), while increasing the number of hyperglycemic events (RR: 1.68; 95 % CI: 1.32, 2.12; P = <0.0001) and hospital readmissions (RR: 1.19; 95 % CI: 1.04, 1.37; P = 0.01). CONCLUSIONS: The results of this meta-analysis demonstrate that corticosteroids yield improved outcomes in CAP patients with regard to reduced mortality and the need for mechanical ventilation. It highlights the need for further large-scale RCTs with the proposed, specific stratifications.
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Corticosteroides , Pneumonia , Humanos , Corticosteroides/uso terapêutico , Respiração Artificial , Pneumonia/tratamento farmacológico , Pneumonia/epidemiologia , Tempo de Internação , Unidades de Terapia IntensivaRESUMO
OBJECTIVE: To determinate the association between of albumin, neutrophil-lymphocyte ratio and lymphocytes (NLR) with clinical stage in cervical cancers. METHODS: Design a retrospective cross-sectional study of consecutive subjects diagnosed with cervical cancer for the first time. The Bethesda system was used for histological diagnosis and the subjects were stratified with the FIGO system, considering stages IA to IIB as localized; while, IIIA and IVB as advanced stages. Albumin, NLR and lymphocytes were evaluated as inflammatory biomarkers and the cut-off points generated by the ROC curves were albumin < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul. The association was calculated by Odds Ratios (OR) with 95% confidence intervals. RESULTS: A total of 152 patients were analyzed, with mean age of 49.3 ± 14.0 years. Epidermoid cancer was the most frequent in 70.6% and 51.3% were classified as advanced clinical stages. A bivariate analysis showed significant relationships between advanced clinical stages and albumin < 3 mg/dL with OR 5.72 (CI95% 2.62-12.4; p < 0.001); for NLR ≥ 2.0 an OR 2.53 (CI95% 1.34-4.89; p = 0.005) and for lymphocytes < 1.2 103/ul of OR 3.39 (CI95% = 1.73-6.65; p < 0.001). CONCLUSIONS: Albumin levels < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul, were associated with advanced stages in subjects with cervical cancer.
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Background: Since the 1990's attempts to favorably modulate nitric oxide (NO) have been unsuccessful. We hypothesized that because NO is lipophilic it would preferentially localize into intravascularly infused hydrophobic nanoparticles, thereby reducing its bioavailability and adverse effects without inhibiting its production. We aimed to determine the efficacy and safety of intravenous infusion of a fluid comprised of hydrophobic phospholipid nanoparticles (VBI-S) that reversibly absorb NO in the treatment of hypotension of patients in severe septic shock. Methods: This is a multicentre, open-label, repeated measures, phase 2a clinical pilot trial done at six hospital centers in the USA. Patients in severe septic shock were enrolled after intravenous fluid therapy had failed to raise mean arterial blood pressure (MAP) to at least the generally accepted level of 65 mmHg, requiring the use of vasopressors. The primary endpoint of this study is the proportion of patients in whom MAP increased by at least 10 mmHg. VBI-S was administered intravenously to patients as boluses of 100 ml, 200 ml, 400 ml, and 800 ml at 999 ml/min until the blood pressure goal was reached after which the infusion was stopped, and the MAP was recorded. All patients who received any volume of VBI-S were included in the primary and safety analysis. The study is registered with ClinicalTrials.gov, NCT04257136. Findings: Between February 17, 2020 and January 3, 2023, 20 eligible patients were enrolled in the study. In all 20 (100%) patients, the goal of increasing MAP by at least 10 mmHg using VBI-S was achieved (p = 0.0087, effect size = 0.654). Mean VBI-S volume required to meet the primary goal was 561.0 ± 372.3 ml. The goal of lowering vasopressor dose was also achieved (p = 0.0017). Within 48 h or less after VBI-S, there was a statistically significant improvement in oxygenation, serum creatinine, clotting variables, procalcitonin, lactic acid, and the sequential organ failure assessment (SOFA) score. At 24 h and 48 h following administration of VBI-S, 12/15 (80%) and 9/12 (75%) patients developed hyperlipidemia, respectively. No severe adverse events of VBI-S were observed, and there were no treatment-related deaths. Interpretation: These preliminary findings suggest the safety and efficacy of VBI-S in treating hypotension in patients with septic shock. However, a definitive mortality benefit cannot be demonstrated without a randomized controlled study. Funding: The Naval Medical Research Command-Naval Advanced Medical Development program via the Medical Technology Enterprise Consortium.
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Importance: Plasma cell orificial mucositis (PCOM) associated with cocaine use is an emerging, rare condition that has become a concern in Spain in recent years. Limited knowledge exists regarding this novel condition. Objectives: To delineate the clinicopathologic characteristics of this emerging entity and establish a novel approach in the differential diagnosis of cocaine-associated lesions. Design, Setting, and Participants: A descriptive, retrospective, multicenter case series of 10 patients diagnosed with cocaine-associated PCOM was conducted in Spain from April 2020 to March 2023. Main Outcomes and Measures: Patient demographic, clinical, histopathologic, and treatment data were collected. Results: A total of 10 patients (6 [60%] male; median [range] age, 45.5 [36-66] years) presenting with exudative ulcerated plaques were identified for this study. The lesions had raised and erythematous edges over the nostril and a median (range) evolution time of 9 (2-24) months. Septal or palate perforations were observed in 4 (40%) of the patients. Biopsies revealed a dense inflammatory infiltrate of plasma cells in the dermis without atypia and with eosinophils. All patients reported recent cocaine use. Three urine tests detected cocaine but found no presence of amphetamines or opiates. Six patients improved with corticosteroid therapy. Up to 60% of patients were lost to follow-up. Conclusions and Relevance: This case series describes the clinicopathologic characteristics of PCOM, an emerging entity associated with cocaine use in Spain, and demonstrates a novel approach in the differential diagnosis of cocaine-associated lesions. To date, cocaine-associated skin lesions have been reported as neutrophilic dermatoses and vasculitis. The appearance of a plasma cell infiltrate changes what has been described in the medical literature so far. PCOM is a benign condition of unknown cause characterized by a proliferative polyclonal plasma cell infiltrate. A comprehensive differential diagnosis workup is required to reach this exclusionary diagnosis. Several irritants have been documented in cases of PCOM, and a hypersensitivity mechanism has been proposed. Since the initial report of cocaine-associated PCOM in Spain, its incidence has experienced a surge in the country. The cause of this phenomenon may be attributed to newly unidentified adulterants. The administration of corticosteroids and discontinuation of cocaine use are the sole treatments that have demonstrated efficacy. Clinicians should be vigilant regarding this emerging condition and conduct inquiries into cocaine use. Additional research is required to clarify the pathophysiology of this emerging condition.
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Cocaína , Mucosite , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Mucosite/patologia , Plasmócitos/patologia , Estudos Retrospectivos , Eritema/patologia , Inflamação/patologia , Cocaína/efeitos adversosRESUMO
BACKGROUND: a significant proportion of octogenarian patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI) with stenting. Dual antiplatelet therapy is recommended in these patients, requiring a period of triple therapy with dual antiplatelet agent plus oral anticoagulation (OAC). Concerns remain regarding the appropriateness of OAC in octogenarians. METHODS: we reviewed 604 patients (15.7% ≥80 years) with AF undergoing PCI. Clinical follow-up was performed, recording any bleeding episode, thrombo-embolism and major adverse cardiac events (MACE = death, acute myocardial infarction and/or revascularisation of target lesion). We compared octogenarian patients in relation to treatment with OAC at discharge. A secondary aim was to compare octogenarian patients with non-octogenarian patients in terms of their clinical and demographic characteristics, management and clinical outcome. RESULTS: among the 604 patients, 95(15.7%) were aged ≥80 years. Octogenarians had a higher median CHADS2 score (2.78 versus 2.01; P < 0.001) and HAS-BLED score (3.05 versus 2.84; P = 0.028). After a follow-up of 17 ± 14 months, all-cause death occurred in 33%, MACE in 44%, and major bleeding in 21%. OAC was associated with less MACE (28.9 versus 58.3%; P = 0.012) and a similar rate of major bleeding. On multivariable analysis, non-use of OAC at discharge was associated with increased MACE (OR = 4.3; 95% CI = 1.3-14.6; P = 0.02). CONCLUSION: octogenarian AF patients undergoing PCI/stenting have a high mortality rate and MACE, which can be reduced by means of OAC therapy.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Stents/efeitos adversos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea/mortalidade , Intervenção Coronária Percutânea/reabilitação , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: The degrees to which residual symptoms in major depressive disorder (MDD) adversely affect patient functioning is not known. This post-hoc analysis explored the association between different residual symptoms and patient functioning. METHODS: Patients with MDD who responded (≥50% on the 17-item Hamilton Rating Scale for Depression; HAMD-17) after 3 months of treatment (624/930) were included. Residual core mood-symptoms (HAMD-17 core symptom subscale ≥1), residual insomnia-symptoms (HAMD-17 sleep subscale ≥1), residual anxiety-symptoms (HAMD-17-anxiety subscale ≥1), residual somatic-symptoms (HAMD-17 Item 13 ≥1), pain (Visual Analogue Scale ≥30), and functioning were assessed after 3 months treatment. A stepwise logistic regression model with normal functioning (Social and Occupational Functioning Assessment Scale ≥80) as the dependent variable was used. RESULTS: After 3 months, 59.5% of patients (371/624) achieved normal functioning and 66.0% (412/624) were in remission. Residual symptom prevalence was: core mood symptoms 72%; insomnia 63%; anxiety 78%; and somatic symptoms 41%. Pain reported in 18%. Factors associated with normal functioning were absence of core mood symptoms (odds ratio [OR] 8.7; 95% confidence interval [CI], 4.6-16.7), absence of insomnia symptoms (OR 1.8; 95% CI, 1.2-2.7), episode length (4-24 weeks vs. ≥24 weeks [OR 2.0; 95% CI, 1.1-3.6]) and better baseline functioning (OR 1.0; 95% CI, 1.0-1.1). A significant interaction between residual anxiety symptoms and pain was found (p = 0.0080). CONCLUSIONS: Different residual symptoms are associated to different degrees with patient functioning. To achieve normal functioning, specific residual symptoms domains might be targeted for treatment.