RESUMO
BACKGROUND: Alpha thalassemia-myelodysplastic syndrome (ATMDS) is one of the possible complications related to the genetic instability typical of clonal hemopoietic disorders such as myelodysplastic syndromes (MDS). Hemoglobin H acquisition, which is hemoglobin without alpha chains and with 4 beta chains is the hallmark of this disease. OBSERVATION: An 86-year-old male with chronic, microcytic anemia was referred due to a fall in his hemoglobin level. The blood smear was remarkable for intense anisocytoses and poikilocytosis. Bone marrow analysis was followed by a diagnosis of MDS with a good prognostic score. Peripheral blood coloration with brilliant cresyl blue showed "golf ball-like" erythrocytes. Hemoglobin electrophoresis is notable for the presence of H hemoglobin. The new generation sequencing confirmed the diagnosis of ATMDS showing a non-sense mutation in the gene ATRX. CONCLUSION: The diagnosis of ATMDS should be considered in the presence of the association of MDS, microcytic anemia and marked blood smear abnormalities such as anisocytosis and poikilocytosis. A little less than 10% of all MDS are complicated by ATMDS.
Assuntos
Síndromes Mielodisplásicas , Talassemia alfa , Masculino , Humanos , Idoso de 80 Anos ou mais , Talassemia alfa/complicações , Talassemia alfa/diagnóstico , Proteína Nuclear Ligada ao X/genética , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , MutaçãoRESUMO
Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.
Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Idoso , Citogenética , Análise Mutacional de DNA , Europa (Continente) , Feminino , Deleção de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Processamento de RNA , Receptor Notch1/genética , Recidiva , Ribonucleoproteína Nuclear Pequena U2/genética , Fatores de Tempo , Proteína Supressora de Tumor p53/genéticaAssuntos
Leucemia Linfocítica Crônica de Células B/genética , Proteína 3 com Repetições IAP de Baculovírus , Estudos de Coortes , Humanos , Proteínas Inibidoras de Apoptose/genética , Fator 88 de Diferenciação Mieloide/genética , Fosfoproteínas/genética , Prognóstico , Fatores de Processamento de RNA , Receptor Notch1/genética , Ribonucleoproteína Nuclear Pequena U2/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína LigasesRESUMO
Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset #1, #2 and #8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset #2 (44%) versus subset #1 and #8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset #2 was only 8%, lower than the frequency observed in either subset #1 or #8 (19% and 14%, respectively; P=0.04 for subset #1 versus #2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically oriented therapy.
Assuntos
Biomarcadores Tumorais/genética , Proteínas Inibidoras de Apoptose/genética , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/genética , Mutação/genética , Fosfoproteínas/genética , Receptor Notch1/genética , Ribonucleoproteína Nuclear Pequena U2/genética , Proteína 3 com Repetições IAP de Baculovírus , Estudos de Coortes , DNA de Neoplasias/genética , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Reação em Cadeia da Polimerase , Prognóstico , Fatores de Processamento de RNA , Taxa de Sobrevida , Ubiquitina-Proteína LigasesRESUMO
The Three Musketeers' slogan of solidarity-"All for one, and one for all"-aptly describes how the emerging science of individualized medicine (IM) promises to transform the value of the medical care we deliver to specific individuals as well as global populations.
Assuntos
Prescrições de Medicamentos , Saúde Global , Informática Médica , Análise de Sequência de DNA , Biotecnologia , Tratamento Farmacológico , Economia , Medicina Baseada em Evidências , Humanos , Modelos Teóricos , Equipe de Assistência ao Paciente , Pobreza , Integração de SistemasRESUMO
An occurrence of multiple chronic lung abscesses managed by lobectomy is described. These abscesses were present for 13 years in the patient, a nonimmunocompromised wood pulp worker. The patient had hemoptysis at presentation. The organism isolated was Ochroconis gallopavum, a dematiaceous fungus known to cause disease in immunocompromised patients and epidemic encephalitis in poultry. The fungus is typically found in warm environments and in decaying compost; for this reason, we postulate that his illness was occupationally acquired.
Assuntos
Abscesso Pulmonar/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Fungos Mitospóricos , Doenças Profissionais/diagnóstico , Madeira , Adulto , Doença Crônica , Hemoptise/microbiologia , Humanos , Abscesso Pulmonar/cirurgia , Pneumopatias Fúngicas/cirurgia , Masculino , Doenças Profissionais/cirurgia , Exposição Ocupacional , Pneumonectomia , Fibrose Pulmonar/microbiologiaRESUMO
Pulmonary arteriovenous fistulas are rare, usually related to the Rendu-Osler-Weber syndrome, and are detected by chest CT scan or pulmonary angiography. In a 14-year-old boy without Rendu-Osler-Weber syndrome, but with clinical evidence of a right-to-left shunt, ancillary diagnostic studies were negative for pulmonary arteriovenous fistulas, and the final diagnosis was made by contrast transesophageal echocardiography. Saline echo-contrast medium injected peripherally was seen emerging from each pulmonary vein and filling the left chambers. These findings, in light of other negative test results, established the diagnosis of diffuse telangiectasias at the capillary level in both lungs. After 6 years of medical therapy, the patient remains cyanotic but functions well.
Assuntos
Meios de Contraste/administração & dosagem , Ecocardiografia Transesofagiana , Pneumopatias/diagnóstico por imagem , Pulmão/irrigação sanguínea , Telangiectasia/diagnóstico por imagem , Adolescente , Diagnóstico Diferencial , Ecocardiografia Transesofagiana/métodos , Humanos , Injeções Intravenosas , Pulmão/diagnóstico por imagem , MasculinoRESUMO
OBJECTIVE: To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS: A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS: A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION: On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Fotorradiação com Hematoporfirina/métodos , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Broncoscopia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Fotorradiação com Hematoporfirina/efeitos adversos , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do TratamentoRESUMO
This report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and "rheumatoid-like" nodules. Two months after the administration of combined-modality therapy for stage IIIA non-small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.
Assuntos
Artrite/complicações , Carcinoma de Células Escamosas/complicações , Neoplasias Pulmonares/complicações , Vasculite/complicações , Anti-Inflamatórios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artrite/patologia , Artrite/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Dedos/patologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Radioterapia Adjuvante , Esteroides , Vasculite/terapiaRESUMO
OBJECTIVE: To characterize the pulmonary hemodynamics and identify predictors of pulmonary hypertension in a group of patients before liver transplantation and to determine whether pulmonary hypertension in these patients is related to survival. MATERIAL AND METHODS: In 362 patients before their first liver transplantation (between 1985 and 1993), the clinical history, laboratory data, and results of pulmonary function tests were recorded. Pulmonary artery (PA) catheterization was performed after induction of anesthesia at the time of transplantation. Monthly follow-up was maintained. RESULTS: A hyperdynamic circulation was often present -- an increased mean cardiac output (7.6 L/min), increased mean PA pressure (20.9 mm Hg), correlation of mean PA pressure with cardiac output (r = 0.25; P<0.001), and decreased mean pulmonary vascular resistance (60 dynes times s/cm5). Mean PA pressures were more than 25 mm Hg in 72 patients (20%). Pulmonary hypertension (defined as mean PA pressure of more than 25 mm Hg and pulmonary vascular resistance in excess of 120 dynes times s/cm5) occurred in 15 patients (4%). Pulmonary function tests revealed obstruction in 7%, restriction in 18%, and low diffusing capacity in 46%. By univariate analysis, lower forced expiratory volume in 1 second, forced vital capacity, and total lung capacity were the only preoperative factors associated with pulmonary hypertension (P<0.05). Survival was significantly lower in patients with acute fulminant hepatitis (P<0.001), the group with the highest mean PA pressure, than in those with other diagnoses. Increased PA pressures or mild to moderate pulmonary hypertension was not found to be associated with a worse survival by univariate or multivariate analysis. CONCLUSION: Increased PA pressure is common in liver transplant patients (20%). "True" pulmonary hypertension occurred in only 4% of our patients and was not associated with an adverse outcome.
Assuntos
Hemodinâmica , Hipertensão Pulmonar/etiologia , Transplante de Fígado/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Hepatopatias/classificação , Hepatopatias/fisiopatologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Pressão Propulsora Pulmonar , Testes de Função Respiratória , Análise de SobrevidaRESUMO
BACKGROUND: Patients who are comatose or semicomatose are at risk of corneal dryness and ulceration. OBJECTIVE: To compare and evaluate the effectiveness of two treatments used for the prevention of corneal epithelial breakdown in critically ill patients. METHODS: A randomized clinical trial was used. The sample consisted of critically ill patients (age, 15-84 years) with a limited or absent blink reflex in a 14-bed general intensive care unit in a large metropolitan teaching hospital. Ninety-six eligible patients were studied; of these, 36 were excluded and data from the remaining 60 patients were analyzed. Patients were randomized to receive methylcellulose lubricating drops every 2 hours (n = 30) or to have their eyes covered with a polyethylene film to create a moisture chamber (n = 30). The patients' corneas were tested daily for epithelial breakdown using fluorescein drops. Patients were studied for a minimum of 48 hours and a maximum of 1 week. RESULTS: Eight of the 30 patients in the lubricating drop group had positive fluorescein staining, compared with one in the moisture chamber group. CONCLUSION: Our results suggest that a moisture chamber is more effective than lubricating drops in preventing corneal epithelial breakdown in critically ill patients with limited or absent blink reflex.
Assuntos
Coma/complicações , Cuidados Críticos , Umidade , Ceratite/prevenção & controle , Lubrificação , Soluções Oftálmicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Piscadela , Distribuição de Qui-Quadrado , Córnea/fisiopatologia , Córnea/ultraestrutura , Cuidados Críticos/economia , Cuidados Críticos/métodos , Humanos , Ceratite/etiologia , Metilcelulose/uso terapêutico , Pessoa de Meia-Idade , Excipientes Farmacêuticos/uso terapêutico , PolietilenosRESUMO
Photodynamic therapy is an investigational treatment of various types of carcinoma. It involves a photosensitizing agent which, when exposed to light of the proper wavelength, forms toxic oxygen radicals that result in cell death. This article describes its current use in the management of bronchogenic carcinoma.
Assuntos
Carcinoma Broncogênico/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Derivado da Hematoporfirina/uso terapêutico , Fotorradiação com Hematoporfirina , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Broncogênico/diagnóstico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , MasculinoRESUMO
The hepatopulmonary syndrome is an uncommon accompaniment of chronic liver disease. The outcome of this disorder after orthotopic liver transplantation is variable. We describe a patient with the hepatopulmonary syndrome who underwent orthotopic liver transplantation for autoimmune hepatitis. Her platypnea and orthodeoxia failed to improve postoperatively. Pulmonary angiography showed large pulmonary arteriovenous shunts that were successfully treated with coil embolotherapy.
Assuntos
Embolização Terapêutica , Hepatopatias/terapia , Transplante de Fígado , Pneumopatias/terapia , Adulto , Angiografia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Doenças Autoimunes/cirurgia , Feminino , Hepatite/cirurgia , Humanos , Circulação Pulmonar , Síndrome , Falha de TratamentoRESUMO
OBJECTIVE: Although the Health Care Financing Administration (HCFA) uses Medicare hospital mortality data as a measure of hospital quality of care, concerns have been raised regarding the validity of this concept. A problem that has not been fully evaluated in these data is the potential confounding effect of illness severity factors associated with referral selection and hospital mortality on comparisons of risk-adjusted hospital mortality. We address this issue. DATA SOURCES AND STUDY SETTING: We analyzed the 1988 Medicare hospitalization data file (MEDPAR). We selected data on patients treated at the two Mayo Clinic-associated hospitals in Rochester, Minnesota, and a group of seven other hospitals that treat many patients from large geographic areas. These hospitals have had observed mortality rates substantially lower than those predicted by the HCFA model for the period 1987-1990. STUDY DESIGN: Using the multiple logistic regression model applied by HCFA to the 1988 data, we evaluated the relationship between distance from patient residence to the admitting hospital and risk-adjusted hospital mortality. PRINCIPAL FINDINGS: Among patients admitted to Mayo Rochester-affiliated hospitals, residence outside Olmsted County, Minnesota was independently associated with a 33 percent lower 30-day mortality rate (p < .001) than that associated with residence in Olmsted County. When patients at Mayo hospitals were stratified by residence (Olmsted County versus non-Olmsted County), the observed mortality was similar to that predicted for community patients (9.6 percent versus 10.2 percent, p = .26), whereas hospital mortality for referral patients was substantially lower than predicted (5.0 percent versus 7.5 percent, p = < .001). After incorporation of the HCFA risk adjustment methods, distance from patient residence to the hospitals was also independently associated with mortality among the Mayo Rochester-affiliated hospitals and seven other referral center hospitals. CONCLUSIONS: The HCFA Medicare hospital mortality model should be used with extreme caution to evaluate hospital quality of care for national referral centers because of residual confounding due to severity of illness factors associated with geographic referral that are inadequately captured in the extant prediction model.
Assuntos
Mortalidade Hospitalar , Hospitais/normas , Medicare/normas , Modelos Estatísticos , Qualidade da Assistência à Saúde , Encaminhamento e Consulta , Idoso , Idoso de 80 Anos ou mais , Centers for Medicare and Medicaid Services, U.S. , Hospitais de Prática de Grupo/normas , Hospitais de Prática de Grupo/estatística & dados numéricos , Humanos , Medicare/estatística & dados numéricos , Minnesota , Encaminhamento e Consulta/estatística & dados numéricos , Características de Residência , Viés de Seleção , Índice de Gravidade de Doença , Estados UnidosRESUMO
The concept of using a stent to maintain patency of a lumen is not new. As early as 1969, stents were being investigated in the peripheral arterial system as a means of preventing restenosis after dilatation by balloon angioplasty (Dotter, 1969). Since then, numerous reports have demonstrated the use of stents in both the peripheral and coronary artery systems (Maass et al., 1982; Dotter et al., 1983; Wright et al., 1985; Palmaz et al., 1987). Concomitant with the investigation of expandable endovascular metal prosthesis has been the development of prosthetic devices for management of tracheobronchial, gastrointestinal, and genitourinary diseases. We will review the use of endoscopically placed prosthetic devices in the management of diseases affecting these systems.
RESUMO
We retrospectively studied 22 patients with hepatopulmonary syndrome (HPS) evaluated at the Mayo Medical Center from 1984 to 1991. All patients had hepatic cirrhosis with clinical evidence of portal hypertension; 13 (59 percent) had severe hypoxemia while breathing room air in the supine position (PaO2 < 60 mm Hg), and 14 of 16 (88 percent) had orthodeoxia breathing room air. On the basis of angiographic observations, we defined type 1 and type 2 patterns of pulmonary vascular abnormalities in HPS. Response to 100 percent oxygen and therapeutic regimens may differ in the angiographic patterns. Substantial deterioration in PaO2 associated with clinically stable hepatic dysfunction was documented in five of seven patients studied with sequential arterial blood gas testing; four subsequently died within 48 months. Overall mortality was 41 percent, occurring a mean of 2.5 years after diagnosis. In 7 of the 22 patients, we prospectively studied the effect of somatostatin analogue given subcutaneously for 4 consecutive days. No significant improvement in PaO2 was documented while breathing room air or 100 percent oxygen (p < 0.05). We conclude that in selected patients with clinically stable hepatic dysfunction and deteriorating oxygenation, the prognosis is poor. Our data in combination with recent surgical reports suggest that liver transplantation may be the treatment of choice in patients with HPS and worsening oxygenation.
Assuntos
Hepatopatias , Pneumopatias , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Adulto , Idoso , Angiografia , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/terapia , Pulmão/irrigação sanguínea , Pneumopatias/sangue , Pneumopatias/diagnóstico , Pneumopatias/diagnóstico por imagem , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Prospectivos , Estudos Retrospectivos , SíndromeRESUMO
Endoscopic therapy for cancer that involves the tracheobronchial tree is currently available for two distinct types of lesions: radiographically occult superficial squamous cell carcinoma and advanced malignant tumors that cause severe airway obstruction. Photodynamic therapy, which uses a photosensitizing agent, is effective for managing early superficial squamous cell carcinoma. Neodymium:yttrium-aluminum-garnet laser therapy has been effective in the palliative management of patients with advanced or recurrent malignant obstructive airway lesions, either alone or in combination with intraluminal radiation therapy. Most recently, endobronchial prosthetic devices (stents) have been used in patients with advanced airway obstruction. The use of each of these modalities in the management of lung cancer is reviewed.