RESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) often has significant diagnostic delay. At present it is not well-known what factors associate with time to diagnosis and if this is associated with survival after the diagnosis. There has also been increasing attention for interstitial lung abnormalities on chest CT-scans. In this study we assessed what factors associate with time to diagnosis in patients with IPF, and whether early stages of pulmonary fibrosis can be seen on chest X-rays prior to the start of symptoms. METHODS: In this retrospective study, 409 Dutch patients with IPF were included. Clinical characteristics, including patient demographics, medical history, time of start of symptoms, time of first visit to pulmonologist, and any previous radiographic imaging reports were collected from patient records. RESULTS: In 96 patients (23%) a chest X-ray was available that had been made prior to the start of symptoms (median of 50.5 months (IQR 26.3-83.3 months)), and this showed potential interstitial lung abnormalities in 56 patients (58%). The median time from the start of symptoms to the final diagnosis was 24.0 months (interquartile range 9.0-48.0 months). In a multivariate model that corrected for diffusion capacity of the lung for carbon monoxide, forced vital capacity, sex, and age at diagnosis, time to diagnosis did not associate with survival (hazard ratio 1.051 (95% CI 0.800-1.380; p = 0.72)). CONCLUSIONS: There is a significant diagnostic delay for patients with IPF, but longer time to diagnosis did not associate with survival. Interstitial lung abnormalities were seen in more than half of the patients in whom a chest X-ray had been made prior to the start of symptoms. This illustrates that a computed tomography scan should be strongly considered for analysis of unexplained abnormalities on a chest X-ray. This could facilitate early detection and possibly prevention of disease progression for patients with pulmonary fibrosis.
Assuntos
Fibrose Pulmonar Idiopática , Anormalidades do Sistema Respiratório , Diagnóstico Tardio , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Estudos Retrospectivos , Raios XRESUMO
PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease, in which inflammation is thought to only play a secondary role. Several factors associated with acute exacerbations of IPF (AE-IPF) have been identified, including infections. This study investigated whether humoral immunodeficiency or increased inflammatory markers at diagnosis were associated with AE-IPF and survival. METHODS: Four-hundred-and-nine patients diagnosed with IPF between 2011 and 2017 were retrospectively included. Immune status investigations at diagnosis included measurement of serum immunoglobulins (available in 38%), leukocyte and lymphocyte subsets in blood and bronchoalveolar lavage (BAL) fluid (available in 58%), as well as response to pneumococcal vaccination (available in 64%). RESULTS: Serum immunoglobulins or IgG subclass levels were below the lower limit of normal in 6%. The response to pneumococcal vaccination was severely impaired in 1%. Thirteen percent of patients developed an AE-IPF (4.7% per year). AE-IPF were associated with elevated lymphocytes in BAL fluid at diagnosis (p = 0.03). Higher serum IgA and IgG at diagnosis were associated with worse survival (p = 0.01; and p = 0.04), as were an increased BAL lymphocyte percentage (p = 0.005), and higher blood leukocytes and neutrophils (p = 0.01; and p = 0.0005). In a multivariate model, only BAL lymphocyte count retained statistical significance (p = 0.007). CONCLUSION: The prevalence of humoral immunodeficiencies was low in patients with IPF and not associated with AE-IPF or survival. Elevated lymphocytes in BAL were associated with the development of AE-IPF and worse survival. Higher serum immunoglobulins and immune cells in blood were also associated with worse survival. The local immune response in the lungs may be a target for future therapies.
Assuntos
Fibrose Pulmonar Idiopática , Humanos , Pulmão , Linfócitos , Neutrófilos , Estudos RetrospectivosRESUMO
AIM: Emergency surgery is a known predictor for 30-day mortality. However, its relationship with long-term mortality is still a matter of debate. The aim of this study was to analyse the effect of emergency surgery compared with elective surgery on long-term survival. METHOD: Data from the Dutch Colorectal Audit and the Dutch Cancer Centre registry of a large nonacademic teaching hospital were used to analyse outcomes of patients who underwent surgery for colon cancer from 2009 until 2017. Univariable and multivariable Cox regression were used to assess the effect of emergency surgery on long-term mortality with adjustment for patient, tumour and treatment characteristics. RESULTS: A total of 1139 patients with a median follow-up of 40 months (interquartile range 23-65 months) were included. Emergency surgery was performed in 158 patients (14%). The 5-year survival after emergency surgery was 46% compared with 72% after elective surgery. After adjusting for baseline differences there was an independent and significant association between emergency surgery and increased long-term mortality (hazard ratio 1.79, 95% CI 1.28-2.51, P = 0.001). CONCLUSION: Emergency surgery for colon cancer seems to lead to a significantly increased risk of long-term mortality compared with elective surgery. Detection and treatment of early symptoms that can lead to emergency surgery might be the way forward.
Assuntos
Colectomia , Neoplasias do Colo , Neoplasias do Colo/cirurgia , Procedimentos Cirúrgicos Eletivos , Emergências , HumanosRESUMO
AIM: Older colorectal cancer (CRC) patients are at increased risk of postoperative morbidity and mortality. Routine postoperative overnight intensive care unit (ICU) admission might reduce this risk. This study aimed to examine the effect of routine overnight ICU admission after CRC surgery on postoperative adverse outcomes and costs in patients aged 80 years or older. METHODS: Patients aged 80 years or older who underwent CRC surgery in our centre were included in this observational cohort study. All patients in the period 2014-2017 with routine overnight ICU admission were assigned to the ICU cohort; all patients in the period 2009-2013 were assigned to the non-ICU cohort. Multivariable logistic regression was performed to compare the primary composite end-point (30-day mortality, serious complications and readmission) between the groups. Cost data from the literature were used to perform a cost analysis. RESULTS: A total of 242 patients were included, 125 in the ICU cohort and 117 in the non-ICU cohort. Routine overnight ICU admission was associated with a reduced risk of the composite end-point (OR 0.44, 95% CI 0.22-0.87, P = 0.02) after adjusting for important confounders. In the ICU cohort 28% of patients experienced ICU events requiring intervention; this was not associated with postoperative morbidity or mortality. The 9% reduction in the incidence of serious complications in the ICU cohort is sufficient to offset the additional costs of routine overnight ICU admission. CONCLUSION: Routine overnight ICU admission after CRC surgery in patients aged 80 years and older is associated with reduced risk of postoperative mortality and morbidity and seems to be cost-effective.
Assuntos
Neoplasias Colorretais , Admissão do Paciente , Idoso , Neoplasias Colorretais/cirurgia , Mortalidade Hospitalar , Humanos , Incidência , Unidades de Terapia Intensiva , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
INTRODUCTION AND AIM: Joint bleeding results in blood-induced arthropathy. We investigate whether a joint bleed alters protease-activated receptor (PAR) expression, and whether treatment with small interfering RNA (siRNA) targeted against PAR1-4 attenuates synovitis and cartilage damage. METHODS: Protease-activated receptor expression was evaluated upon a joint bleed in haemophilic mice and in humans. In addition, mice with a joint bleed were randomized between treatment with PAR1-4 siRNA or control and evaluated for the presence of synovitis and cartilage damage. Also, human cartilage was transfected with PAR1-4 siRNA or control, and evaluated for plasmin-induced cartilage damage. RESULTS: Following a joint bleed, we observed an increase in synovial PAR1, -2 and -4 expression, and an increase in chondrocyte PAR2 and -3 expression in mice (all P < 0.05). Also an increase in synovial PAR1 and chondrocyte PAR4 expression in patients was observed (both P < 0.05). Treatment of a joint bleed in haemophilic mice with PAR1-4 siRNA attenuates synovitis and cartilage damage (both P < 0.01). Treatment of human cartilage tissue explants with PAR1-4 siRNA reduced plasmin-induced cartilage damage (P < 0.01). CONCLUSION: This study demonstrates that synovial and chondrocyte PAR expression is altered upon a joint bleed, and that treatment with PAR1-4 siRNA attenuates synovitis and plasmin-induced cartilage damage.
Assuntos
Cartilagem Articular/patologia , Inativação Gênica , Hemofilia A/complicações , Hemorragia/complicações , Receptores Ativados por Proteinase/deficiência , Receptores Ativados por Proteinase/genética , Sinovite/genética , Animais , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Fibrinolisina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hemorragia/genética , Hemorragia/patologia , Humanos , Camundongos , RNA Interferente Pequeno/genética , Sinovite/complicações , Sinovite/patologiaRESUMO
Protease-activated receptors (PARs) are stimulated by proteolytic cleavage of their extracellular domain. Coagulation proteases, such as FVIIa, the binary TF-FVIIa complex, free FXa, the ternary TF-FVIIa-FXa complex and thrombin, are able to stimulate PARs. Whereas the role of PARs on platelets is well known, their function in naïve monocytes and peripheral blood mononuclear cells (PBMCs) is largely unknown. This is of interest because PAR-mediated interactions of coagulation proteases with monocytes and PBMCs in diseases with an increased activation of coagulation may promote inflammation. To evaluate PAR-mediated inflammatory reactions in naïve monocytes and PBMCs stimulated with coagulation proteases. For this, PAR expression at protein and RNA level on naïve monocytes and PBMCs was evaluated with flow cytometry and RT-PCR. In addition, cytokine release (IL-1ß, IL-6, IL-8, IL-10, TNF-α) in stimulated naïve and PBMC cell cultures was determined. In this study, it is demonstrated that naïve monocytes express all four PARs at the mRNA level, and PAR-1, -3 and -4 at the protein level. Stimulation of naïve monocytes with coagulation proteases did not result in alterations in PAR expression or in the induction of inflammation involved cytokines like interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8, interleukin-10 or tumour necrosis factor-α. In contrast, stimulation of PBMCs with coagulation proteases resulted in thrombin-mediated induction of IL-1ß and IL-6 cytokine production and PBMC cell proliferation in a PAR-1-dependent manner. These data demonstrate that naïve monocytes are not triggered by coagulation proteases, whereas thrombin is able to elicit pro-inflammatory events in a PAR-1-dependent manner in PBMCs.
Assuntos
Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Receptor PAR-1/genética , Trombina/farmacologia , Adulto , Fatores de Coagulação Sanguínea/farmacologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Masculino , Monócitos/citologia , Monócitos/metabolismo , Peptídeo Hidrolases/farmacologia , Receptor PAR-1/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Recurrent joint bleeding is the most common manifestation of severe haemophilia resulting in haemophilic arthropathy (HA). Iron plays a central role in the pathogenesis of the two main features of HA: synovitis and cartilage destruction. The aim of this study was to investigate the synovial presence of the iron regulator proteins ferroportin (FPN), hepcidin, haemoglobin scavenger receptor CD163 (CD163), feline leukaemia virus subgroup C (FLVCR), and heme carrier protein 1 (HCP-1). A comparison of the expression in HA with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls (HC) is made. Synovial expression of iron regulators was investigated by immunohistochemistry in human synovial tissue and in a murine haemophilia model. We demonstrate for the first time the synovial presence of the investigated iron regulator proteins. Expression of the iron regulator proteins FPN, CD163, FLVCR, and HCP-1 was enhanced in HA in comparison to RA, OA, and HC synovium. In addition, in a murine haemophilia model of acute joint bleeding, synovial expression of FPN, CD163, and HCP-1 was increased. In both human and murine experiment, synovial expression of hepcidin was not altered. These findings indicate the presence of iron regulator proteins in the synovium, demonstrate an enhanced expression of FPN, CD163, FLVCR, and HCP-1 in HA, and suggest a synovial adaptation mechanism to maintain synovial iron homeostasis in HA.
Assuntos
Artrite Reumatoide/metabolismo , Hemartrose/metabolismo , Hemofilia A/metabolismo , Proteínas Reguladoras de Ferro/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/metabolismo , Regulação para Cima , Animais , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Hemartrose/patologia , Hemofilia A/patologia , Humanos , Ferro/metabolismo , Camundongos , Osteoartrite/patologia , Membrana Sinovial/patologiaRESUMO
BACKGROUND: Currently, outcomes of Multiple Sclerosis (MS) are not standardized and it is unclear which outcomes matter most to people living with MS. A consensus between patients and healthcare professionals on which outcomes to measure and how, would facilitate a move towards value-based MS care. OBJECTIVE: to develop an internationally accepted, patient-relevant Standard Outcome Set for MS (S.O.S.MS). METHODS: A mixed-method design was used, including a systematic literature review, four patient focus groups (n=30) and a RAND-modified Delphi process with seventeen MS experts of five disciplines from seven countries (the Netherlands, United States of America, Portugal, Ireland, India, New Zealand, Switzerland and Turkey). RESULTS: A standard outcome set for MS was defined, consisting of fourteen outcomes divided in four domains: disease activity (n=3), symptoms (n=4), functional status (n=6), and quality of life (n=1). For each outcome, an outcome measure was selected and the measurement protocol was defined. In addition, seven case-mix variables were selected. CONCLUSION: This standard outcome set provides a guideline for measuring outcomes of MS in clinical practice and research. Using this set to monitor and (inter)nationally benchmark real-world outcomes of MS can support improvement of patient value and ultimately guide the transition towards value-based MS care.
Assuntos
Esclerose Múltipla , Qualidade de Vida , Humanos , Esclerose Múltipla/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Resultado do Tratamento , Assistência Centrada no PacienteRESUMO
AIMS: The aims of the study are to investigate the prevalence of diabetes in patients with cystic fibrosis compared with patients without cystic fibrosis, and its impact on the outcome after lung transplantation. METHODS: Data were reviewed from 77 lung transplantation recipients in our centre between 2001 and 2010; 43 patients had cystic fibrosis and 34 patients had other lung diseases (no cystic fibrosis). To define diabetes, we used the American Diabetes Association definition. RESULTS: Before lung transplantation, diabetes was diagnosed in 63% of patients with cystic fibrosis and 6% of patients without cystic fibrosis (P<0.001). In both groups, approximately 60% of the patients at risk developed new-onset diabetes after transplantation. The mortality in patients with cystic fibrosis was higher in patients with diabetes diagnosed before lung transplantation compared with those without (44 vs. 6%, P=0.04). Diabetes remained an independent factor in multivariate analyses. CONCLUSIONS: Diabetes diagnosed before lung transplantation has a negative effect on survival after lung transplantation in patients with cystic fibrosis. Pre-existing diabetes is common in patients with cystic fibrosis, in contrast to patients without cystic fibrosis. Development of new-onset diabetes after transplantation is similar in both groups.
Assuntos
Fibrose Cística/complicações , Diabetes Mellitus/diagnóstico , Transplante de Pulmão/estatística & dados numéricos , Adulto , Estudos de Coortes , Fibrose Cística/mortalidade , Fibrose Cística/cirurgia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/mortalidade , Feminino , Humanos , Incidência , Pneumopatias/complicações , Pneumopatias/mortalidade , Pneumopatias/cirurgia , Masculino , Complicações Pós-Operatórias/mortalidade , Período Pré-Operatório , Prevalência , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Hepatitis C infection is a major comorbidity in patients with inherited bleeding disorders. Successful antiviral treatment leads to a reduction in liver fibrosis, as shown by liver biopsies. Liver stiffness measurement (LSM) is a non-invasive method of assessing liver fibrosis. The aim of this cohort study was to evaluate the long-term effect of successful antiviral treatment, using LSM, in HCV-infected patients with inherited bleeding disorders. The LSM were performed in 2005 (LSM 1) and 2009 (LSM 2) in 39 patients who were successfully treated for HCV. The change in liver fibrosis between LSM 1 and 2 was assessed. The median duration of HCV infection was 28.8 years. A total of 22 patients (56%) underwent successful antiviral treatment before LSM 1 (group 1), and 17 patients between LSM 1 and LSM 2 (group 2). The median time since antiviral treatment was 8.8 years in group 1 and 2.5 years in group 2. In group 1, the median results of LSM 1 and 2 were similar (6.0 vs. 5.6 kPa, P-value 0.36), so overall, patients remained stable. In three patients in this group, all treated more than 15 years ago, an increase of liver stiffness was shown. Group 2 showed a significant improvement in median LSM results (10.3 vs. 6.1 kPa, P-value <0.01), with decrease of liver stiffness in 82%. Even after a long HCV infection duration, successful antiviral treatment led to a significant improvement of fibrosis, measured by LSM, mainly in the first few years after completing treatment.
Assuntos
Antivirais/uso terapêutico , Transtornos Herdados da Coagulação Sanguínea/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/patologia , Fígado/patologia , Adulto , Estudos de Coortes , Técnicas de Imagem por Elasticidade/métodos , Feminino , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Adulto JovemRESUMO
The incidence of haemophilic arthropathy in multiple joints decreased due to treatment with clotting factor. Nowadays patients are enabled to live a rather normal life, resulting in more (sports) trauma-induced arthropathy in isolated joints like the ankle. As surgical treatment options, fusion of the tibiotalar joint and total ankle replacement are available. Both standard treatments have complications and therefore an alternative treatment is desired. In this study, treatment of haemophilic ankle arthropathy with joint distraction was explored. Three patients with haemophilic ankle arthropathy were treated with joint distraction using an Ilizarov external fixator. Clinical outcomes like function, participation and pain were evaluated in retrospect with three different questionnaires: haemophilia activities list, impact on participation and autonomy and the Van Valburg questionnaire. Structural changes were assessed blinded on X-ray by the Pettersson score and ankle images digital analysis (AIDA) and by an MRI score. All three patients were very satisfied with the clinical outcome of the procedure. They reported a clear improvement for self-perceived functional health, participation in society and autonomy and pain. Partial ankle joint mobility was preserved in the three patients. The Pettersson score remained the same in one patient and slightly improved in the two other patients, while joint space width measured by AIDA and the MRI score demonstrated improvement for all three patients after ankle distraction. This study suggests that joint distraction is a promising treatment for individual cases of haemophilic ankle arthropathy, without additional risk of bleedings during treatment.
Assuntos
Hemofilia A/complicações , Hemofilia B/complicações , Artropatias/etiologia , Artropatias/cirurgia , Adolescente , Adulto , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/fisiopatologia , Articulação do Tornozelo/cirurgia , Fixadores Externos , Hemartrose/etiologia , Hemartrose/cirurgia , Humanos , Artropatias/diagnóstico por imagem , Artropatias/fisiopatologia , Masculino , Radiografia , Amplitude de Movimento ArticularRESUMO
BACKGROUND: Patients receiving chemotherapy are at increased risk for influenza virus infection. Little is known about the preferred moment of vaccination during chemotherapy. PATIENTS AND METHODS: Breast cancer patients received influenza vaccination during FEC (5-fluorouracil, epirubicin and cyclophosphamide)-containing chemotherapy regimens. Patients were randomised for early (day 4) or late (day 16) vaccination during the chemotherapy cycle. Influenza virus-specific antibody titres were determined before and 3 weeks after vaccination by haemagglutination inhibition. RESULTS: We included 38 breast cancer patients (20 in the early and 18 in the late group) and 21 healthy controls. The overall patient group had significant lower responses to the vaccine compared with healthy controls. Patients vaccinated at day 4 tended to have higher antibody titres as compared with patients vaccinated at day 16, although the difference in post-vaccination titres is not statistically significant. Geometric mean titres post-vaccination for day 4 versus day 16 were 63.7 versus 29.5 (H3N2), 28.2 versus 19.6 (H1N1) and 29.8 versus 16.0 (B/Brisbane), respectively. CONCLUSIONS: Patients on chemotherapy have significantly lower responses to influenza virus vaccination compared with healthy controls. Vaccination early during the chemotherapy cycle induces better responses than does vaccination at day 16 of the cycle. Follow-up studies are needed to confirm this effect.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adulto , Idoso , Anticorpos Antivirais/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/virologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Esquemas de Imunização , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Pessoa de Meia-IdadeRESUMO
The role of individual cytokines and polymorphisms in pneumonia has been described, but the relationship between different cytokines and polymorphisms in relation to causative microorganisms, antibiotics, corticosteroids and clinical course has not. This study questions the relationship between cytokines, polymorphisms and clinical characteristics of pneumonia. Patients diagnosed with pneumonia were included in the study. Serum cytokine levels were measured during hospital stay, genotyping was performed, causative microorganisms were identified and patients were monitored throughout the hospital stay. In 201 patients with pneumonia interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8 and IL-10 acted as acute phase proteins. After admission, the levels of these cytokines decreased rapidly. Single nucleotide polymorphisms did not influence cytokine production and were not associated with clinical outcome. Cytokine serum levels were significantly higher in patients with pneumococcal pneumonia. The decrease in levels of cytokines was independently influenced by the start of corticosteroid therapy. IL-1RA, IL-6, IL-8 and IL-10 are acute phase proteins, independent of genotype. Their levels are influenced by the nature of the causative microorganism and the start of corticosteroids therapy.
Assuntos
Infecções Comunitárias Adquiridas/sangue , Citocinas/sangue , Pneumonia Bacteriana/sangue , Proteínas de Fase Aguda/genética , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/genética , Citocinas/genética , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-6/sangue , Interleucina-6/genética , Interleucina-8/sangue , Interleucina-8/genética , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Recent initiation of proton-pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonisation of the oropharynx by gastrointestinal bacteria. The aim of this study was to assess the causal pathway by considering microbial aetiology of pneumonia and indications for initiation of PPI treatment. This was a population-based, case-control study with 430 cases with pneumonia and 1,720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed. Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.1, 95% CI 1.4-7.1). Oropharyngeal bacteria were evenly distributed among current users, past users and nonusers of PPIs (p=0.41). Gastrointestinal bacteria were identified in only five (1.2%) patients with pneumonia (two current users and three nonusers). Excluding patients who were possibly prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings. This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment has recently been started. Neither protopathic bias nor shifts in microbial aetiology seem to explain the association.
Assuntos
Orofaringe/microbiologia , Pneumonia Bacteriana/etiologia , Inibidores da Bomba de Prótons/efeitos adversos , Bactérias/crescimento & desenvolvimento , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pneumonia Bacteriana/microbiologia , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de RiscoRESUMO
The classification of haemophilia originates from 1950s and has been adopted unchallengedly by the ISTH in 2001. The aim of this study was: does the current classification compare onset of bleeding and age at first treatment, as well as annual joint bleeding frequency according to baseline FVIII activity? Data on age and reason of diagnosis, onset of treatment, onset of bleeding and bleeding frequency from 411 patients with haemophilia A born after 1970 were collected. Data were analysed according to base-line FVIII activity levels. Age at diagnosis, onset of bleeding and start of treatment according to FVIII activity were compared with the current classification. Overall, the distinction between severe and non-severe haemophilia was clear. The distinction between mild and moderate haemophilia was more difficult, mostly due to the wide variability in the group of patients with moderate haemophilia. Patients with severe haemophilia experienced their milestones like diagnosis, first treatment and joint bleed earliest, mostly as infants aged 0-3 years, whereas patients with moderate haemophilia reached these milestones around toddler age, 2-7 years, and patients with mild haemophilia reached them when they were in elementary school, around the ages of 5-14 years. This study confirms the clinical distinction between severe and non-severe haemophilia A. However, the group of moderate haemophilia patients showed a wide variability, warranting close follow-up and individualized treatment.
Assuntos
Hemofilia A/classificação , Índice de Gravidade de Doença , Adolescente , Adulto , Fatores Etários , Criança , Estudos de Coortes , Fator VIII/metabolismo , Hemartrose/epidemiologia , Hemofilia A/diagnóstico , Hemofilia A/metabolismo , Humanos , Fenótipo , Adulto JovemRESUMO
The purpose of this study was to determine the quantity and quality of antibodies against the meningococcal serogroup C (MenC) conjugated vaccine in asplenic patients. In 116 asplenic patients, antibody concentrations (IgG) were measured against meningococcal serogroup C before and after immunisation. Of MenC-specific IgG, both antibody avidity and subclasses of IgG1 and IgG2 were determined. The mean MenC IgG concentration rose from 0.16 µg/mL prior to vaccination to 3.69 µg/mL 3 weeks post-vaccination, with 67% of patients reaching the threshold of ≥ 2.0 µg/mL. The mean IgG concentration at 35 weeks post-vaccination was 3.10 µg/mL. IgG2 concentrations increased more than IgG1. Marginal avidity maturation was seen. Hypo-responders to the first MenC vaccine (IgG anti-MenC ≤ 2.0 µg/mL) were offered a booster dose. After revaccination, 59% reached the chosen IgG threshold. The IgG concentration rose from 0.29 to 1.12 µg/mL, with an increase in the IgG1/IgG2 ratio. Avidity indices remained below 33%. In asplenic patients, the quantity and quality of antibodies produced after one dose of conjugated MenC vaccination is lower than that observed in previous studies in healthy adults. Booster vaccination does, indeed, lead to a rise in IgG geometric mean concentrations (GMCs), but does not lead to higher avidity of antibodies.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Meningocócicas/imunologia , Baço/anormalidades , Adulto , Idoso , Idoso de 80 Anos ou mais , Afinidade de Anticorpos , Feminino , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Masculino , Vacinas Meningocócicas/administração & dosagem , Pessoa de Meia-Idade , Países Baixos , Fatores de TempoRESUMO
INTRODUCTION: Bowel obstruction patients are at increased risk of emergency surgery and have poor nutritional and physical conditions. These patients could benefit from prehabilitation and prevention of emergency surgery. This study assessed the effect of a multimodal obstruction treatment for bowel obstruction patients in colorectal surgery on the risk of emergency surgery and postoperative morbidity and mortality. MATERIALS AND METHODS: This multicenter observational cohort study included all consecutive bowel obstruction patients who received obstruction treatment (obstruction protocol) in the period 2019-2020 in two Dutch hospitals. Benign and malignant causes of bowel obstruction were included. Treatment consisted of 1. dietary adjustments, 2. postponing surgery for three weeks, 3. laxatives, and 4. prehabilitation. We compared emergency surgery and postoperative morbidity and mortality rates to known rates from the literature. RESULTS: Eighty-nine patients were included: obstruction treatment was successful in 77 patients (87%) who underwent elective surgery and unsuccessful in 12 patients (13%) who underwent emergency surgery. Sixty-six (74%) had colorectal cancer, and 22 (25%) had benign disease. Thirty-day mortality of 0% in our study was significantly lower than the national average of 4% in colorectal cancer patients in the Netherlands (p = 0.049). Anastomotic leakage rate was 3%, severe complications (Clavien-Dindo ≥ III) 8%, and bowel perforation 0%. These rates did not differ significantly from rates reported in literature. CONCLUSION: The obstruction treatment prevented emergency surgery in most patients with bowel obstruction and reduced postoperative morbidity and mortality. The obstruction treatment seems to be a safe and efficient alternative to emergency surgery.
Assuntos
Neoplasias Colorretais/complicações , Cirurgia Colorretal/métodos , Obstrução Intestinal/terapia , Perfuração Intestinal/etiologia , Complicações Pós-Operatórias/etiologia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Cirurgia Colorretal/efeitos adversos , Terapia Combinada , Doença de Crohn/complicações , Dieta , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Diverticulite/complicações , Procedimentos Cirúrgicos Eletivos , Emergências , Humanos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Laxantes/uso terapêutico , Mortalidade , Países Baixos , Estado Nutricional , Exercício Pré-Operatório , Período Pré-Operatório , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Recently, ocrelizumab (Ocrevus®) was approved for the treatment of primary progressive multiple sclerosis (PPMS) based on data from the ORATORIO clinical trial. Real-world data about the clinical effectiveness of ocrelizumab has yet to be gathered. OBJECTIVE: The aim of this study was to provide data about the clinical effectiveness of ocrelizumab for patients diagnosed with PPMS in a real-world setting. METHODS: We conducted a retrospective cohort study of all patients with PPMS who started ocrelizumab treatment (n = 21) in St. Antonius Hospital (Utrecht/Nieuwegein, the Netherlands) between April 2018 and December 31, 2018. Primary outcome was pre- versus post-ocrelizumab disability worsening rate (from 96 weeks prior to first ocrelizumab administration up to 24 weeks post first ocrelizumab administration). RESULTS: Disability worsening rate while on treatment significantly differed (lower) from disability worsening rate in pre-treatment period (Z = -2.81, p ≤ .01). Three out of 17 patients showed a clinically relevant improvement in disability status after treatment start. CONCLUSION: Ocrelizumab can stabilize disability progression in patients with PPMS. Some patients even showed a clinically relevant improvement in disability status. Further research should help to identify which patients benefit most from ocrelizumab.
RESUMO
Mannose-binding lectin (MBL) is a pattern recognition receptor of the complement system and plays an important role in innate immunity. Whether or not MBL acts as an acute-phase response protein in infection has been an issue of extensive debate, because MBL responses have shown a high degree of heterogeneity. Single nucleotide polymorphisms (SNPs) in the promoter (wild-type Y versus X) and exon 1 (A versus 0) of the MBL2 gene can lead to MBL deficiency. This study investigated the influence of SNPs in the promoter and exon 1 of the MBL2 gene on the acute-phase responsiveness of MBL in 143 patients with community-acquired pneumonia. Acute-phase reactivity was observed only in MBL-sufficient genotypes (YA/YA, XA/YA, XA/XA and YA/0). In patients with wild-type exon 1 genotype A/A, positive acute-phase responses were associated with the presence of the YA haplotype and negative responses with its absence. Genotypes YA/0 and XA/XA produced equal levels of MBL in convalescence. In the acute phase, however, patients with genotype XA/XA displayed negative acute-phase responses more often than those with genotype YA/0. Correlation of MBL and C-reactive protein levels in the acute phase of pneumonia also depended upon the MBL2 genotype. In conclusion, acute-phase responsiveness of MBL was highly dependent upon the MBL2 genotype. These data suggest that heterogeneity in protein responses in the acute phase of disease should always be viewed in the light of possible influences of genetic differences in both structural and regulatory parts of the gene.
Assuntos
Reação de Fase Aguda/imunologia , Lectina de Ligação a Manose/imunologia , Pneumonia/imunologia , Doença Aguda , Reação de Fase Aguda/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Infecções Comunitárias Adquiridas/genética , Infecções Comunitárias Adquiridas/imunologia , Feminino , Genótipo , Humanos , Masculino , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/genética , Pessoa de Meia-Idade , Pneumonia/genética , Estudos ProspectivosRESUMO
A 45-year-old woman, known to have a congenital exstrophy ofthe bladder, for which she underwent a ureterosigmoidostomy in her infancy, presented with fever. This was due to pyelonephritis, from which she recovered with antibiotic therapy. During colonoscopy a carcinoma of the sigmoid was found at the level of the anastomosis of the ureters. Patients with a ureterosigmoidostomy have a one hundred-fold increased risk of colon carcinoma compared to the general population. The development of malignant tumours as a long-term complication of this procedure is linked with the frequent contact between intestinal tissue and urine. Periodical colonoscopy of these patients is advised.