BACKGROUND Cardiac surgery patients have some of the highest reported incidence and prevalence of pressure injuries (PI). A growing subset of cardiac surgery include patients with end-stage heart failure who undergo ventricular assist device (VAD) or total artificial heart (TAH) surgery. The risk of PI and their natural history of development in this population are unknown and the specific risk factors for PI development remain unexplored. OBJECTIVES To perform a systematic review of the literature to identify the incidence and risk factors of PI development in patients undergoing VAD-TAH surgery and thereby inform study design and variables in an eight-year retrospective study of all patients undergoing VAD-TAH surgery at a large academic university medical center. METHODS The preferred reporting items for systematic reviews and meta-analyses or PRISMA statement guided this systematic review. Quality of evidence was determined using the Johns Hopkins Nursing Evidence-Based Practice Rating Scale. Two reviewers independently appraised manuscripts matching the eligibility criteria for study inclusion. Four databases including PubMed, CINAHL, Web of Science, Google Scholar, and hand searches of journals based on reference lists from included studies were utilized. Initial results of this primary search revealed zero studies that met inclusion and this search methodology was confirmed by medical librarian consultation. Therefore, a follow up retrospective study was necessary to identify incidence of PI in the VAD-TAH population. However, a secondary search, dropping keywords of VAD-TAH and instead focusing on studies of on-pump cardiac surgery and mixed surgical studies where cardiac surgery patients were included, was conducted to establish variables to guide a retrospective study of all VAD-TAH surgeries between 2010-2018. The retrospective study evaluated the incidence of pressure ulcers by case, patient and incidence density for each of the respective 1000 patient days during the study period. Univariate statistics are reported by four different VAD-TAH devices. Variables significant in bivariate analysis were entered in a stepwise logistic regression model. RESULTS In the systematic review, 312 articles were identified from the databases with eight additional articles from hand searches. Following abstract review, 208 were excluded for not meeting inclusion criteria or study quality metrics. 77 articles were read in full, with 61 excluded, leaving 16 articles for inclusion. 31 risk factors were identified for PI development in on-pump cardiac surgery patients with 11 risk factors which were identified as significant in multivariate analysis for inclusion in the retrospective study.

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in serum via enzyme-linked immunoassay (ELISA). Stool was collected for 16s rRNA sequencing, SCFAs (gas chromatography), and proximate analyses (PA). PA analyses: Bomb calorimetry (kcal), soxhlet for lipids, kjeldhal for protein, and fiber. Dietary intake by food frequency questionnaires (FFQ). HIV+ males had significantly higher H:W and hepatic steatosis (pPrevotella and Lachnospiraceae compared to HIV- males. Additionally, HIV+ males had significantly higher central obesity and hepatic steatosis. In a retrospective analysis, all HIV+ men were men that have sex with men (MSM). These findings support differences in intestinal microbiome and SCFAs, and measures of altered lipid metabolism between HIV+ and HIV- males. These findings lay the framework for investigations into intestinal microbiome, SCFAs and metabolism in HIV+ MSM.

L’objectif de cette thèse était d’étudier la distribution, les déterminants et les conséquences des délais diagnostiques des cancers de l’enfant, par une revue systématique de la littérature, une analyse des plaintes déposées en France et au Canada et par des études ad hoc en population sur les tumeurs ayant des délais particulièrement longs : le médulloblastome et le sarcome d’Ewing.La revue systématique n’a pas retrouvé de diminution significative de la longueur des délais au cours du temps. Les délais longs étaient associés à un âge élevé, au type histologique et à la localisation de la tumeur. Les relations entre délai et gravité de la maladie étaient variables. Seul un tiers des conclusions des expertises judiciaires (n = 56) étaient concordantes avec les données de la littérature.Le délai diagnostique médian des enfants atteints de médulloblastome en Ile-de-France (n = 166) était de 65 jours. Les délais longs étaient associés paradoxalement à des métastases moins fréquentes et à une histologie favorable, mais pas à la survie ni aux séquelles.Le délai diagnostique médian des enfants atteints de sarcome d’Ewing en France (n = 436) était de 70 jours. Les délais longs, liés à un âge élevé et à la localisation de la tumeur, n’étaient pas associés au volume tumoral, à la présence de métastases, à l’opérabilité ni à la survie.Pour certaines tumeurs, une association entre délais diagnostiques et gravité est établie (rétinoblastome) ou hautement probable. Pour d’autres, l’absence d’association démontrée permettrait de dédramatiser la perception de leurs conséquences, sans dispenser d’essayer de réduire ces délais, notamment pour en atténuer les conséquences psychologiques. / The aim of this thesis was to study the distribution, determinants and consequences of time to diagnosis of cancer in children, through a systematic review of the literature and an analysis of lawsuits in France and Canada, and two population-based studies of tumors with particularly long diagnosis delays: medulloblastoma and Ewing sarcoma.The systematic review did not identify any significant decreases in time to diagnosis during the studies. Long times to diagnosis were associated with older age, histological type and location of the tumor. Associations between time to diagnosis and severity of the disease varied. Only a third of the court-appointed experts (n = 56) provided testimony concordant with the available medical literature.The median time to diagnosis of children with medulloblastoma in the area of Paris (n = 166) was 65 days. Diagnosis delays were paradoxically associated with less frequent metastasis and favorable histology, but not with survival, or sequelae.The median time to diagnosis of children with Ewing sarcoma in France (n = 436) was 70 days. Diagnosis delays, related with older age and tumor location, were not associated with tumor size, presence of metastasis, surgical outcome, or survival.For some tumors, an association between time to diagnosis and severity of the disease is well established (e.g. retinoblastoma), or highly probable. For others, the lack of demonstrated associations could tone down the perception of the supposed consequences of diagnosis delays - but does not exempt from trying to reduce them, in order to alleviate their psychological consequences.

Introdução: A esclerodermia é rara doença do tecido conectivo que se manifesta através da esclerose cutânea e variável acometimento sistêmico. Duas categorias de esclerodermia são conhecidas: esclerose sistêmica, caracterizada por esclerose cutânea e acometimento visceral e a esclerodermia localizada ou morfeia que classicamente apresenta evolução benigna e autolimitada, confinada a pele e/ou tecidos subjacentes. Estudos recentes demonstram que a forma localizada possa eventualmente apresentar acometimento de órgãos internos e morbidade variável. Objetivo: Neste estudo objetivamos determinar as características demográficas, a prevalência de manifestações sistêmicas e alterações laboratoriais, bem como a associação com doenças autoimunes, em pacientes com esclerodermia da face. Métodos: Pacientes com esclerodermia localizada, incluindo os casos de esclerodermia em golpe de sabre, síndrome de Parry-Romberg e morfeia em placas com acometimento facial, foram avaliados e submetidos à investigação neurológica, incluindo exame clínico neurológico e ressonância magnética de crânio, e avaliação oftalmológica. Após 3 anos, o subgrupo de pacientes disponível para seguimento foi ressubmetido à ressonância magnética. Resultados: Foram estudados 34 pacientes com esclerodermia localizada da face. Deste total, 64,7% apresentavam uma ou mais manifestações extracutâneas, sendo cefaleia a queixa mais frequente, encontrada em 61,8% dos pacientes. Dos 23 pacientes submetidos à avaliação neurológica, 56,5% apresentaram alterações neurológicas possivelmente associadas à esclerodermia. Alterações à ressonância magnética foram observadas em 50% dos casos. O achado mais frequente foi a presença de lesões parenquimatosas com alteração de sinal em 50% dos pacientes. Dos pacientes que apresentavam alteração neurológica, 80% também apresentavam alguma alteração à ressonância magnética. Doze pacientes foram ressubmetidos a novo exame após 3 anos. Em todos os pacientes os achados de imagem se mantiveram inalterados. Durante esse intervalo de 3 anos, 25% dos pacientes apresentaram sinais de atividade da esclerodermia. Quanto à avaliação oftalmológica, 67,9% dos pacientes avaliados apresentaram alteração, sendo os achados mais frequentes a ocorrência de alterações orbiculares da esclerodermia (20,6%) e xeroftalmia (10,7%). Conclusão: Pacientes com esclerodermia localizada da face apresentam alta prevalência de alterações neurológicas e oftalmológicas. Baseado nestes achados, sugerimos que todos os casos de esclerodermia localizada da face devam ser detalhadamente examinados quanto à presença de alterações sistêmicas / Introduction: Scleroderma is a rare connective tissue disease that manifests as skin sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement and localized scleroderma or morphea which classically presents benign evolution and selflimited, confined to the skin and / or underlying tissue. Recent studies show that the localized form may possibly course with involvement of internal organs and variable morbidity. Objective: This study aimed to determine the demographic characteristics, the prevalence of systemic manifestations and laboratory findings, as well as the association with autoimmune diseases, in patients with scleroderma of the face. Methods: Patients with localized scleroderma, including cases of scleroderma en coup de sabre, Parry-Romberg syndrome and morphea plaque with facial involvement were evaluated and underwent neurological examination, including neurologic examination and magnetic resonance imaging, and ophthalmology evaluation. After 3 years, the subgroup of patients available for follow-up was subjected again to MRI. Results: We studied 34 patients with localized scleroderma of the face. Of this total, 64,7% had one or more extracutaneous manifestation, headache being the most frequent complaint found in 61,8% of patients. Of the 23 patients undergoing neurological evaluation, 56,5% had neurological changes possibly associated with scleroderma. MRI changes were observed in 50% of cases. The most frequent was the presence of parenchymal lesions with signal alteration in 50% of patients. Of the patients who had neurological deficits, 80% also had a change to MRI. Twelve patients were subjected again to another MRI scan after 3 years. In all patients, imaging findings were unchanged. During this interval of 3 years, 25% of patients showed signs of activity of scleroderma. As for ophthalmologic evaluation, 67,9% of patients showed abnormalities, with the most frequent findings being the occurrence of orbicular changes of scleroderma (20.6%) and xerophthalmia (10.7%). Conclusion: Patients with localized scleroderma face have a high prevalence of neurological and ophthalmological changes. Based on these findings, we suggest that all cases of localized scleroderma of the face should be thoroughly examined for the presence of systemic changes

Introdução: Este estudo foi realizado com o intuito de avaliar efeitos da acupuntura sobre os pacientes com asma leve e moderada persistentes com o uso de beta-2 agonista ou corticoide inalatório. Métodos e casuística: Trata-se de um estudo prospectivo, duplo-cego, randomizado e cruzado com dois braços. Os 74 pacientes com diagnóstico de asma leve/moderada, de acordo com a classificação de GINA 2002/2003, foram divididos em dois grupos, sendo 31 do Grupo I, e 43 do Grupo II inicialmente. Foram realizadas consultas médicas e exames que incluíram espirometria, citologia de escarro induzido, NO expirado, preenchimento de escala de sintoma, questionários de qualidade de vida de asma e de SF 36, e realização de peak-flow, dependendo da Fase do protocolo. A Fase I constituiu-se dos exames pré-intervenção. Na Fase II, foram realizadas 10 sessões de Acupuntura Real no Grupo I e 10 sessões de Acupuntura Sham no Grupo II, na Fase III, houve 4 semana de washout, na Fase IV, houve a troca de técnicas de acupuntura, sendo uma sessão por semana e, na Fase V, realização dos exames. Resultados: Não há diferença nos critérios de avaliação no pré-tratamento entre dois grupos, com exceção de maior celularidade inflamatória no Grupo II. No entanto, houve uma redução significativa de eosinófilos (p = 0,035) e neutrófilos (p = 0,047), e aumento de macrófagos (p = 0,001), melhora da medida de volume do peak-flow (p = 0,01) na fase IV do Grupo II. No Grupo I, na avaliação de escala de sintomas diária, havia menor uso de medicação de resgate (p = 0,043) na Fase II, e, depois de receber a Acupuntura Sham na Fase IV, havia menos tosse (p = 0,007), menos chiado (p = 0,037), menos dispneia (p < 0,001) e menor uso de medicação de resgate (p < 0,001). No Grupo II, após receber o tratamento com a Acupuntura Sham na Fase II, houve diminuição de tosse (p = 0,037), de chiado (p = 0,013) e de dispneia (p = 0,014), e, na Fase IV, havia menos tosse (p = 0,040), sibilos (p = 0,012), dispneia (p < 0,001) e menos despertares noturnos (p = 0,009). Nos questionários de qualidade de vida de asma e de SF 36, foram encontrados alguns aspectos de melhora significantes na Acupuntura Sham dos dois grupos em relação à Fase I, mas os resultados da Acupuntura Real tiveram maiores índices de melhora em relação aos resultados da Acupuntura Sham nos dois grupos. Mas não há diferença significativa entre os dois na qualidade de vida de SF 36. Entretanto, não houve alteração de avaliação de espirometria e de óxido nítrico expirado. Conclusão: Este estudo demonstrou que o uso de Acupuntura Real num grupo de pacientes com a celularidade mais inflamatória teve melhor resultados de sintomas diários, tais como dispneia e despertar noturno, de medida de volume de peak-flow matutina, e de avaliação de qualidade de vida em asma e SF36, além da diminuição quantitativa de neutrófilos e de eosinófilos, com aumento de macrófagos, que justificam os efeitos anti-inflamatórios e imunitários. A acupuntura é uma terapia segura, não havendo nenhum efeito colateral observado neste projeto que possa interferir com a vida cotidiana e pode ser de grande auxílio no alívio de sintomas, com melhora de qualidade de vida e, possivelmente, pode ter uma ação na modulação do processo inflamatório de vias aéreas / Introduction: This survey has been conducted in order to evaluate the effects of acupuncture in patients with persistent mild and moderate asthma (according to GINA criteria 2003), using beta agonist and/or inhaled glucocorticoid. Methods and patients: This is a prospective, double blinded, randomized and cross-over study with two branches: 74 patients diagnosed with mild and moderate asthma were divided into two groups: Group I with 31, initiating with real acupuncture and Group II, starting with sham acupuncture. Medical interview and laboratory tests including spirometry, induced sputum citology, exhaled NO measurement, quality of life questionnaire (SF-36 and QQL), besides, daily symptom scores and measurement of peak-flow were performed, in the beginning of the study, and in the end of each phase of treatment. Phase I: laboratory tests and other qualitative measurements. There were 10 real acupuncture weekly sessions to Group I and 10 sham acupuncture sessions to Group II in Phase II. On the other hand, in the Phase IV, there was an exchange between Group I and Group II, which was receiving real acupuncture started to receive sham, and vice-versa, the number of sessions remained the same (10 weekly sessions). Phase III, during the interval between Phase II and Phase IV, there was an interval of 4 weeks of washout. Phase V: laboratory tests and other qualitative measurements. Results: There was no difference beween both the groups in all criteria of evaluation pré treatment, with only na exception: in the Group II there was large inflammatory cell counts. However, there was a significant reduction in eosinophils (p = 0.035) and neutrophils (p = 0.047), and increase of macrophages (p = 0.001), improved peak-flow measurement in the morning (p = 0.01) in Group II (started with sham) in Phase IV. In Daily Symptons Score, there was a significant reduction in use of rescue medication (p = 0.043) in Group I (real acupuncture) in Phase II and after received sham acupuncture (Phase IV), there were less cough (p = 0.007), less wheezing (p = 0.037), less dyspnea (p < 0.001) e less use of rescue medication (p < 0.001). In Group II, after received sham (Phase II), there were less cough (p = 0.037), less wheezing (p = 0.013) and less dyspnea (p = 0.014). In Phase IV, less cough (p = 0.040), wheezing (p = 0.012), dyspnea (p < 0.001) and less nocturnal awakening (p = 0.009). In the questionnaires of quality of life SF-36 and QQL, several domains were found to be improved after received sham acupuncture in both groups, comparing phase II against phase I, but the results found after received real acupuncture were better than sham in both groups. Although there was no statistic difference between both groups. However, there was no difference in exhaled NO and spirometry measurement. Conclusion: This survey demonstrated that the use of real acupuncture in a group of patients with large inflammatory cells counts could have contributed to reduce symptoms, improve quality of life, improved peak-flow measurement in the morning and reduced inflammatory cells count in induced sputum, therefore, acupuncture is a safe healing techniques, presented no adverse effects observed in this study, and could of great help in treatment of patients with mild and moderate asthma

Introdução: A esclerodermia é rara doença do tecido conectivo que se manifesta através da esclerose cutânea e variável acometimento sistêmico. Duas categorias de esclerodermia são conhecidas: esclerose sistêmica, caracterizada por esclerose cutânea e acometimento visceral e a esclerodermia localizada ou morfeia que classicamente apresenta evolução benigna e autolimitada, confinada a pele e/ou tecidos subjacentes. Estudos recentes demonstram que a forma localizada possa eventualmente apresentar acometimento de órgãos internos e morbidade variável. Objetivo: Neste estudo objetivamos determinar as características demográficas, a prevalência de manifestações sistêmicas e alterações laboratoriais, bem como a associação com doenças autoimunes, em pacientes com esclerodermia da face. Métodos: Pacientes com esclerodermia localizada, incluindo os casos de esclerodermia em golpe de sabre, síndrome de Parry-Romberg e morfeia em placas com acometimento facial, foram avaliados e submetidos à investigação neurológica, incluindo exame clínico neurológico e ressonância magnética de crânio, e avaliação oftalmológica. Após 3 anos, o subgrupo de pacientes disponível para seguimento foi ressubmetido à ressonância magnética. Resultados: Foram estudados 34 pacientes com esclerodermia localizada da face. Deste total, 64,7% apresentavam uma ou mais manifestações extracutâneas, sendo cefaleia a queixa mais frequente, encontrada em 61,8% dos pacientes. Dos 23 pacientes submetidos à avaliação neurológica, 56,5% apresentaram alterações neurológicas possivelmente associadas à esclerodermia. Alterações à ressonância magnética foram observadas em 50% dos casos. O achado mais frequente foi a presença de lesões parenquimatosas com alteração de sinal em 50% dos pacientes. Dos pacientes que apresentavam alteração neurológica, 80% também apresentavam alguma alteração à ressonância magnética. Doze pacientes foram ressubmetidos a novo exame após 3 anos. Em todos os pacientes os achados de imagem se mantiveram inalterados. Durante esse intervalo de 3 anos, 25% dos pacientes apresentaram sinais de atividade da esclerodermia. Quanto à avaliação oftalmológica, 67,9% dos pacientes avaliados apresentaram alteração, sendo os achados mais frequentes a ocorrência de alterações orbiculares da esclerodermia (20,6%) e xeroftalmia (10,7%). Conclusão: Pacientes com esclerodermia localizada da face apresentam alta prevalência de alterações neurológicas e oftalmológicas. Baseado nestes achados, sugerimos que todos os casos de esclerodermia localizada da face devam ser detalhadamente examinados quanto à presença de alterações sistêmicas / Introduction: Scleroderma is a rare connective tissue disease that manifests as skin sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement and localized scleroderma or morphea which classically presents benign evolution and selflimited, confined to the skin and / or underlying tissue. Recent studies show that the localized form may possibly course with involvement of internal organs and variable morbidity. Objective: This study aimed to determine the demographic characteristics, the prevalence of systemic manifestations and laboratory findings, as well as the association with autoimmune diseases, in patients with scleroderma of the face. Methods: Patients with localized scleroderma, including cases of scleroderma en coup de sabre, Parry-Romberg syndrome and morphea plaque with facial involvement were evaluated and underwent neurological examination, including neurologic examination and magnetic resonance imaging, and ophthalmology evaluation. After 3 years, the subgroup of patients available for follow-up was subjected again to MRI. Results: We studied 34 patients with localized scleroderma of the face. Of this total, 64,7% had one or more extracutaneous manifestation, headache being the most frequent complaint found in 61,8% of patients. Of the 23 patients undergoing neurological evaluation, 56,5% had neurological changes possibly associated with scleroderma. MRI changes were observed in 50% of cases. The most frequent was the presence of parenchymal lesions with signal alteration in 50% of patients. Of the patients who had neurological deficits, 80% also had a change to MRI. Twelve patients were subjected again to another MRI scan after 3 years. In all patients, imaging findings were unchanged. During this interval of 3 years, 25% of patients showed signs of activity of scleroderma. As for ophthalmologic evaluation, 67,9% of patients showed abnormalities, with the most frequent findings being the occurrence of orbicular changes of scleroderma (20.6%) and xerophthalmia (10.7%). Conclusion: Patients with localized scleroderma face have a high prevalence of neurological and ophthalmological changes. Based on these findings, we suggest that all cases of localized scleroderma of the face should be thoroughly examined for the presence of systemic changes

Introdução: Este estudo foi realizado com o intuito de avaliar efeitos da acupuntura sobre os pacientes com asma leve e moderada persistentes com o uso de beta-2 agonista ou corticoide inalatório. Métodos e casuística: Trata-se de um estudo prospectivo, duplo-cego, randomizado e cruzado com dois braços. Os 74 pacientes com diagnóstico de asma leve/moderada, de acordo com a classificação de GINA 2002/2003, foram divididos em dois grupos, sendo 31 do Grupo I, e 43 do Grupo II inicialmente. Foram realizadas consultas médicas e exames que incluíram espirometria, citologia de escarro induzido, NO expirado, preenchimento de escala de sintoma, questionários de qualidade de vida de asma e de SF 36, e realização de peak-flow, dependendo da Fase do protocolo. A Fase I constituiu-se dos exames pré-intervenção. Na Fase II, foram realizadas 10 sessões de Acupuntura Real no Grupo I e 10 sessões de Acupuntura Sham no Grupo II, na Fase III, houve 4 semana de washout, na Fase IV, houve a troca de técnicas de acupuntura, sendo uma sessão por semana e, na Fase V, realização dos exames. Resultados: Não há diferença nos critérios de avaliação no pré-tratamento entre dois grupos, com exceção de maior celularidade inflamatória no Grupo II. No entanto, houve uma redução significativa de eosinófilos (p = 0,035) e neutrófilos (p = 0,047), e aumento de macrófagos (p = 0,001), melhora da medida de volume do peak-flow (p = 0,01) na fase IV do Grupo II. No Grupo I, na avaliação de escala de sintomas diária, havia menor uso de medicação de resgate (p = 0,043) na Fase II, e, depois de receber a Acupuntura Sham na Fase IV, havia menos tosse (p = 0,007), menos chiado (p = 0,037), menos dispneia (p < 0,001) e menor uso de medicação de resgate (p < 0,001). No Grupo II, após receber o tratamento com a Acupuntura Sham na Fase II, houve diminuição de tosse (p = 0,037), de chiado (p = 0,013) e de dispneia (p = 0,014), e, na Fase IV, havia menos tosse (p = 0,040), sibilos (p = 0,012), dispneia (p < 0,001) e menos despertares noturnos (p = 0,009). Nos questionários de qualidade de vida de asma e de SF 36, foram encontrados alguns aspectos de melhora significantes na Acupuntura Sham dos dois grupos em relação à Fase I, mas os resultados da Acupuntura Real tiveram maiores índices de melhora em relação aos resultados da Acupuntura Sham nos dois grupos. Mas não há diferença significativa entre os dois na qualidade de vida de SF 36. Entretanto, não houve alteração de avaliação de espirometria e de óxido nítrico expirado. Conclusão: Este estudo demonstrou que o uso de Acupuntura Real num grupo de pacientes com a celularidade mais inflamatória teve melhor resultados de sintomas diários, tais como dispneia e despertar noturno, de medida de volume de peak-flow matutina, e de avaliação de qualidade de vida em asma e SF36, além da diminuição quantitativa de neutrófilos e de eosinófilos, com aumento de macrófagos, que justificam os efeitos anti-inflamatórios e imunitários. A acupuntura é uma terapia segura, não havendo nenhum efeito colateral observado neste projeto que possa interferir com a vida cotidiana e pode ser de grande auxílio no alívio de sintomas, com melhora de qualidade de vida e, possivelmente, pode ter uma ação na modulação do processo inflamatório de vias aéreas / Introduction: This survey has been conducted in order to evaluate the effects of acupuncture in patients with persistent mild and moderate asthma (according to GINA criteria 2003), using beta agonist and/or inhaled glucocorticoid. Methods and patients: This is a prospective, double blinded, randomized and cross-over study with two branches: 74 patients diagnosed with mild and moderate asthma were divided into two groups: Group I with 31, initiating with real acupuncture and Group II, starting with sham acupuncture. Medical interview and laboratory tests including spirometry, induced sputum citology, exhaled NO measurement, quality of life questionnaire (SF-36 and QQL), besides, daily symptom scores and measurement of peak-flow were performed, in the beginning of the study, and in the end of each phase of treatment. Phase I: laboratory tests and other qualitative measurements. There were 10 real acupuncture weekly sessions to Group I and 10 sham acupuncture sessions to Group II in Phase II. On the other hand, in the Phase IV, there was an exchange between Group I and Group II, which was receiving real acupuncture started to receive sham, and vice-versa, the number of sessions remained the same (10 weekly sessions). Phase III, during the interval between Phase II and Phase IV, there was an interval of 4 weeks of washout. Phase V: laboratory tests and other qualitative measurements. Results: There was no difference beween both the groups in all criteria of evaluation pré treatment, with only na exception: in the Group II there was large inflammatory cell counts. However, there was a significant reduction in eosinophils (p = 0.035) and neutrophils (p = 0.047), and increase of macrophages (p = 0.001), improved peak-flow measurement in the morning (p = 0.01) in Group II (started with sham) in Phase IV. In Daily Symptons Score, there was a significant reduction in use of rescue medication (p = 0.043) in Group I (real acupuncture) in Phase II and after received sham acupuncture (Phase IV), there were less cough (p = 0.007), less wheezing (p = 0.037), less dyspnea (p < 0.001) e less use of rescue medication (p < 0.001). In Group II, after received sham (Phase II), there were less cough (p = 0.037), less wheezing (p = 0.013) and less dyspnea (p = 0.014). In Phase IV, less cough (p = 0.040), wheezing (p = 0.012), dyspnea (p < 0.001) and less nocturnal awakening (p = 0.009). In the questionnaires of quality of life SF-36 and QQL, several domains were found to be improved after received sham acupuncture in both groups, comparing phase II against phase I, but the results found after received real acupuncture were better than sham in both groups. Although there was no statistic difference between both groups. However, there was no difference in exhaled NO and spirometry measurement. Conclusion: This survey demonstrated that the use of real acupuncture in a group of patients with large inflammatory cells counts could have contributed to reduce symptoms, improve quality of life, improved peak-flow measurement in the morning and reduced inflammatory cells count in induced sputum, therefore, acupuncture is a safe healing techniques, presented no adverse effects observed in this study, and could of great help in treatment of patients with mild and moderate asthma

BackgroundThe prompt seeking of medical care after the onset of symptoms suggestive of acute coronary syndromes (ACS)/acute myocardial infarction (AMI) is associated with the receipt of coronary reperfusion therapy, and effective cardiac medications in patients with an ACS/AMI and is crucial to reducing mortality and the risk of serious clinical complications in these patients. Despite declines in important hospital complications and short-term death rates in patients hospitalized with an ACS/AMI, several patient groups remain at increased risk for these adverse outcomes, including women and the elderly. However, recent trends in age and sex differences in extent of pre-hospital delay, hospital management practices, and short-term outcomes associated with ACS/AMI remain unexplored. The objectives of this study were to examine the overall magnitude, and changing trends therein, of age and sex differences in duration of pre-hospital delay (1986-2005), hospital management practices (1999-2007), and short-terms outcomes (1975-2005) in patients hospitalized with ACS/AMI. MethodsData from 13,663 residents of the Worcester, MA, metropolitan area hospitalized at all greater Worcester medical centers for AMI 15 biennial periods between 1975 and 2005 (Worcester Heart Attack Study), and from 50,096 patients hospitalized with an ACS in 106 medical centers in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007 were used for this investigation. Results In comparison with men years, patients in other age-sex strata exhibited significantly longer pre-hospital delay, with the exception of women < 65 years; had a significantly lower odds of receiving aspirin, angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers, statins, and undergoing coronary artery bypass graft surgery (CABG) surgery or percutaneous coronary intervention (PCI), and were significantly more likely to develop atrial fibrillation, cardiogenic shock, heart failure, and to die during hospitalization and in the first 30 days after admission. There was a significant interaction between age and sex in relation to the use of several medications and the development of several of these outcomes; in patients Conclusions Our results suggest that the elderly were more likely to experience longer prehospital delay, were less likely to be treated with evidence-based treatments during hospitalization for acute coronary syndrome, and were more likely to develop adverse outcomes compared to younger persons. Younger women were less likely to be treated with effective treatments and were more likely to develop adverse outcomes compared with younger men while there was no sex difference in these outcomes. Interventions targeted at older patients, in particular, are needed to encourage these high-risk patients to seek medical care promptly to maximize the benefits of currently available treatment modalities. More targeted treatment approaches during hospitalization for ACS/AMI for younger women and older patients are needed to improve their hospital prognosis.

Sepsis is the leading cause of death among critically ill patients and the 10th most common cause of death overall in the United States. The mortality rates increase with severity of the disease, ranging from 15% for sepsis to 60% for septic shock. Patient with sepsis can present varied clinical symptoms depending on the personal predisposition, causal microorganism, organ system involved, and disease severity. To facilitate sepsis diagnosis, the first sepsis consensus definitions was published in 1991 and then updated in 2001. Early recognition of a sepsis patient followed with timely and appropriate treatment and management strategies have been shown to significantly reduce sepsis-related mortality, and allows care to be provided at lower costs. Despite the rapid progress in the knowledge of pathophysiological mechanisms of sepsis and its treatment in the last two decades, identifying patient with sepsis and therapeutic approaches to sepsis and its complications remains challenging to critical care clinicians. Hence, the objectives of this thesis were to 1) evaluate the test characteristics of the two sepsis consensus definitions and delineate the differences in patient profile among patients meeting or not meeting sepsis definitions; 2) determine the relationship between the changes in several physiological parameters before sepsis onset and sepsis, and to determine whether these parameters could be used to identify sepsis in critically ill adults; 3) evaluate the effect of corticosteroids therapy on patient mortality. Data used in this thesis were prospectively collected from an electronic medical record system for all the adult patients admitted into the seven critical care units (ICUs) in a tertiary medical center. Besides analyzing data at the ICU stay level, we investigated patient information in various time frames, including 24-hour, 12-hour, and 6-hour time windows. In the first study of this thesis, the 1991 sepsis definition was found to have a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which was 96.9% and 58.3%, respectively. The areas under the ROC curve for the two consensus definitions were similar, but less than optimal. The sensitivity and area under the ROC curve of both definitions were lower at the 24-hour time window level than those of the unit stay level, though the specificity increased slightly. At the time window level, the 1991 definitions performed slightly better than the 2001 definition. In the second study, minimum systolic blood pressure performed the best, followed by maximum respiratory rate in discriminating sepsis patients from SIRS patients. Maximum heart rate and maximum respiratory rate can differentiate sepsis patients from non-SIRS patients fairly well. The area under ROC of the combination of five physiological parameters was 0.74 and 0.90 for comparing sepsis to non-infectious SIRS patients and comparing sepsis to non-SIRS patients, respectively. Parameters typically performed better in 24-hour windows compared to 6-hour or 12-hour windows. In the third study, significantly increased hospital mortality and ICU mortality were observed in the group treated with low-dose corticosteroids than the control group based on the propensity score matched comparisons, and multivariate logistic regression analyses after adjustment for propensity score alone, covariates, or propensity score (in deciles) and covariates. This thesis advances the existing knowledge by systemically evaluating the test characteristics for the 1991 and 2001 sepsis consensus definitions, delineating physiological signs and symptoms of deterioration in the preceding 24 hours prior to sepsis onset, assessing the prediction performances of single or combined physiological parameters, and examining the use of corticosteroids treatment and survival among septic shock patients. In addition, this thesis sets an innovative example on how to use data from electronic medical records as these surveillance systems are becoming increasingly popular. The results of these studies suggest that a more parsimonious set of definitional criteria for sepsis diagnosis are needed to improve sepsis case identification. In addition, continuously monitored physiological parameters could help to identify patients who show signs of deterioration prior to developing sepsis. Last but not least, caution should be used when considering a recommendation on the use of low dose corticosteroids in clinical practice guidelines for the management of sepsis.

The alarming rate of increase in incidence and prevalence of the type 2 diabetes mellitus has prompted intense research on understanding the pathogenesis of the type 2 diabetes. It is observed that the development of type 2 diabetes is preceded by a state of insulin resistance and obesity. Previous studies have suggested that the obesity induced insulin resistance may be mediated by elevated levels of circulating free fatty acids (FFAs). The increase in circulating levels of FFAs may be contributed by the release of FFAs from stored triglycerides (TG) in adipocytes via lipolysis. It is hypothesized that the decrease in levels of circulating FFAs by sequestration and storage of FFAs in adipocytes may prevent deleterious effects of FFAs on insulin sensitivity. Recently our lab and others have shown that the storage of TG in adipocytes is promoted by a novel protein, Fat Specific Protein 27 (FSP27). Although, these studies also revealed FSP27 to be a lipid droplet associated protein that suppresses lipolysis to enhance TG accumulation in adipocytes, the role of FSP27 in lipolysis remains largely undetermined. Therefore, this study investigates the role and regulation of FSP27 in adipocytes in both the basal state, as well as during lipolysis. The studies presented here show FSP27 to be a remarkably short-lived protein (half-life=15 min) due to its rapid ubiquitination and proteasomal degradation. Thus, I tested the hypothesis that lipolytic agents like the cytokine, TNF-α and the catecholamine isoproterenol modulate FSP27 protein levels to regulate FFA release. Consistent with this concept, TNF-α markedly decreased FSP27 mRNA and protein along with lipid droplet size as it increased lipolysis in cultured adipocytes. Similarly, FSP27 depletion using siRNA mimicked the effect of TNF-α to enhance lipolysis, while maintaining stable FSP27 protein levels by expression of HA epitope-tagged FSP27 blocked TNF-α mediated lipolysis. In contrast, the robust lipolytic action of isoproterenol is paradoxically associated with increases in FSP27 protein and a delayed degradation rate that corresponds to decreased ubiquitination. This catecholamine-mediated increase in FSP27 abundance, probably a feedback mechanism to restrain excessive lipolysis by catecholamines, is mimicked by forskolin or 8-Bromo-cAMP treatment, and prevented by Protein Kinase A (PKA) inhibitor KT5720 or PKA depletion using siRNA. These results show that isoproterenol stabililizes FSP27 via the canonical PKA pathway and increased cAMP levels. However, the work presented here also suggests that FSP27 does not get phosphorylated in response to isoproterenol treatment, and the stabilization of FSP27 is independent of isoproterenol mediated lipolysis. The data presented in this thesis not only identifies the regulation of FSP27 as an important intermediate in mechanism of lipolysis in adipocytes in response to TNF-α and isoproterenol, but also suggests that FSP27 may be a possible therapeutic target to modulate lipolysis in adipocytes.