RESUMO
In this case report, we describe the case of a 50-year-old woman referred by her general practitioner to a pulmonologist in order to investigate persistent fever and elevation of C-reactive protein despite antibiotic treatment following a respiratory infection. The patient was examined extensively, during which rheumatology, gastroenterology, nephrology, ophthalmology, laboratory and imaging tests were performed. Due to a rapid progression of renal insufficiency with active urinary sediment, the patient was referred for a renal biopsy, which confirmed tubulointerstitial nephritis, followed by a diagnosis of bilateral anterior uveitis two months later - genetic testing was also conducted, which confirmed the diagnosis of tubulointerstitial nephritis with uveitis syndrome. Steroid treatment brought about a gradual reduction of proteinuria and a stabilisation of renal function.
Assuntos
Nefrite Intersticial , Uveíte , Feminino , Humanos , Pessoa de Meia-Idade , Uveíte/complicações , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Nefrite Intersticial/complicações , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/tratamento farmacológico , Glucocorticoides , SíndromeRESUMO
Chronic pancreatitis (CP) is a serious condition with a great impact on the quality of life, and it can lead to some serious long-term consequences such as pancreatic cancer or secondary diabetes mellitus. Associated pancreatic exocrine insufficiency leads to malnutrition with weight loss; however, the main symptom of the disease is abdominal pain, often very severe. The primary treatment option for painful CP is pharmacotherapy (pancreatic enzyme replacement therapy, analgesics). If this is not effective, CP can be treated via endoscopy, extracorporeal shockwave lithotripsy (ESWL), their combination, or surgery. We present a case of painful chronic obstructive pancreatitis in a patient successfully treated with ESWL in combination with endoscopy.
Assuntos
Cálculos , Litotripsia , Humanos , Cálculos/cirurgia , Ductos Pancreáticos , Resultado do Tratamento , Colangiopancreatografia Retrógrada EndoscópicaRESUMO
BACKGROUND: Clear cell renal carcinoma (ccRC) accounts for 65-70% of renal carcinomas with peak occurrence at the 6th and 7th age decade, predominantly in males. At the time of diagnosis, especially pulmonary metastases can be found in one-third of patients. There have also been described as late metastases for several decades after nephrectomy. In our case report, clinical course indicated primary lung tumour. Histological differential diagnosis included malignant pleural mesothelioma, lung adenocarcinoma and squamous cell carcinoma with clear cell differentiation or primary clear cell adenocarcinoma of the lung. However, using immunohistochemistry, all these possible diagnoses were excluded. CASE REPORT: We present a case of 62-year old man with 3 months history of progressive dyspnea accompanied with a cough and recurrent pleural effusions. PET/CT scan revealed metastatic tumour spread with right-sided pleural thickening, multiple pulmonary tumour foci, mediastinal, cervical, abdominal para-aortic and pelvic lymph node involvement and skeletal metastasis. The patient died one day after administration of palliative chemotherapy. The autopsy showed the majority of changes in the right hemithorax, was caused by a diffuse yellowish, extremely tough tumour infiltrating parietal and visceral pleura with adhesions and obliteration of truncus pulmonalis. In left lung and both renal cortices we could see scant nodules, mimicking primary lung tumour metastasis. In close proximity to the left renal hilum we found unusual homogeneous white round to oval tissue of 80 × 86 × 72mm in diameter, with identical histological pattern. Extensive immunohistochemical profile (positivity of CK18, PAX8, vimentin, androgen receptor, napsin A; negativity of mesothelial markers, TTF-1, CK7, CK20, CDX-2, CD10, PSA, CK34B12 and PAS-D) was compatible with metastatic ccRC. CONCLUSION: We present an extremely rare case of morphologically verified metastatic ccRC without evidence of primary lesion in the kidneys. There is speculated the possibility of spontaneous regression of primary tumour. In our case, however, we cannot exclude the possibility of generalized primary tumour of ectopic kidney. This hypothesis is based on the finding of isolated tumour mass adjacent to left renal hilum.
Assuntos
Carcinoma de Células Renais/secundário , Diagnóstico Diferencial , Neoplasias Renais/patologia , Neoplasias Pulmonares/patologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Evolução Fatal , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ßlactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Gestão de Antimicrobianos , Biomarcadores , Monitoramento de Medicamentos , Humanos , Unidades de Terapia Intensiva , Choque Séptico/tratamento farmacológico , beta-Lactamas/farmacocinética , beta-Lactamas/uso terapêuticoRESUMO
INTRODUCTION: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. METHODS: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. RESULTS: The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0-2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). CONCLUSION: GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. TRIAL REGISTRATION: EudraCT-Nr. 2005-003201-81.
RESUMO
Silicosis, caused by inhaling dust containing free crystalline silica, typically has a chronic course, with the numbers of silicosis patients declining globally. Much rarer are the acute and subacute forms. Presented is a case of severe subacute (accelerated) silicosis. The condition resulted from ~2 years of very intense exposure without appropriate personal protective equipment while sandblasting. The patient's initial symptoms were progressive cough, dyspnoea and weight loss. Given his occupational history, typical clinical manifestations and radiological findings, an initial diagnosis of accelerated silicosis was proposed and histologically confirmed. The patient was a candidate for lung transplantation. The case demonstrates a rare but largely preventable disease with serious health effects and a poor prognosis.
Assuntos
Silicose/complicações , Adulto , Tosse/etiologia , Dispneia/etiologia , Humanos , Masculino , Exposição Ocupacional/efeitos adversos , Pletismografia/métodos , Dióxido de Silício/efeitos adversos , Silicose/etiologiaAssuntos
Analgésicos/farmacologia , Anticonvulsivantes/sangue , Dipirona/farmacologia , Epilepsia/sangue , Ácido Valproico/sangue , Idoso , Analgésicos/uso terapêutico , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Dipirona/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Humanos , Masculino , Ácido Valproico/farmacocinética , Ácido Valproico/uso terapêuticoRESUMO
The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).
Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Sepse/diagnóstico , Sepse/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Farmacorresistência Bacteriana , Humanos , Unidades de Terapia Intensiva , Sepse/microbiologia , Sepse/mortalidade , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológicoRESUMO
OBJECTIVE: We present a case of peritoneal tuberculosis of young woman with focus on difficult diagnosis of this low incidence disease in developed countries. DESIGN: Case report. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital, Olomouc. Department of Obstetric and Gynaecology, Nový Jicín Hospital. Department of Pulmonary Diseases and Tuberculosis, Faculty Hospital, Olomouc. Department of Pathology nad Molecular Medicine, Faculty Hospital, Olomouc. Department of Micobiology, Faculty Hospital, Olomouc. CASE REPORT: Peritoneal tuberculosis is an uncommon site of extrapulmonary infection caused by Mycobacterium tuberculosis. Diagnosis is often difficult and because of its nonspecific clinical, laboratory and radiological findings, the disease may be mistaken as ovarian malignancy. We present a case of 28 years old woman with ascites, enlarged lymphonodes, elevated Ca 125 and unusuall adnexal masses on PET/CT in ovarian locality. The diagnosis of tuberculosis in our case was made by laparoscopy and cultivation of Mycobacterium tuberculosis. CONCLUSION: In women with ascites and Ca 125 elevation, the posibility of TB infection should be, despite the low incidence of this disease in developed countries, still considered.
Assuntos
Laparoscopia , Peritonite Tuberculosa/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Ascite/diagnóstico por imagem , Ascite/patologia , Antígeno Ca-125/sangue , Diagnóstico Diferencial , Feminino , Humanos , Peritônio/diagnóstico por imagem , Peritônio/patologia , Peritonite Tuberculosa/diagnóstico por imagemRESUMO
BACKGROUND: Ready to use caspofungin infusion bags are centrally prepared in the Hospital Pharmacy, University Hospital of Heidelberg, for economic reasons and possibly occurring problems with drug shortages. The aim of this study was a quality control of the in-house preparation of caspofungin infusion bags and the preparation process. Caspofungin concentration with regard to chemical stability and antifungal activity of caspofungin preparations were defined as quality parameters. METHODS: Three caspofungin infusion bags (50 mg in 100 mL 0.9% sodium chloride) were examined every seven days for a total of four weeks. Chemical stability of caspofungin solutions was analyzed using a validated high performance liquid chromatography (HPLC) method. Antifungal activity was assessed by microdilution tests according to the EUCAST protocol. Additionally, concentration and sterility were determined in returned caspofungin infusion bags. RESULTS: The amount of caspofungin in the infusion solutions still exceeded 90% after four weeks (2-8 °C). Antifungal activity was consistent over 28 days with a MIC ≤2 mg/L for different Candida spp. In returned infusion bags, caspofungin concentration was found to be ≥90% in 12 out of 13 bags and sterility was given in all preparations. CONCLUSION: These results show that chemical stability of caspofungin infusion solutions (50 mg/100 mL) can be guaranteed for four weeks at 2-8 °C and are confirmed by corresponding results regarding sterility and antifungal activity.
Assuntos
Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Equinocandinas/administração & dosagem , Lipopeptídeos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacologia , Caspofungina , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Equinocandinas/química , Equinocandinas/farmacologia , Infusões Parenterais , Lipopeptídeos/química , Lipopeptídeos/farmacologia , Testes de Sensibilidade Microbiana , Soluções Farmacêuticas , Cloreto de Sódio/química , Fatores de TempoRESUMO
BACKGROUND: In view of increasing rates of bacterial resistance and Clostridium difficile infections efforts to enhance appropriate and intelligent antibiotic prescribing have become important. A prerequisite is the availability of reliable antibiotic use data. So far antibiotic consumption data in this country had only a very limited coverage of acute care hospitals. METHODS: We obtained drug dispensing data from 109 German acute care hospital pharmacies and calculated yearly antibiotic use density values stratified for hospital size and type of serviceâ /â department. Antibiotic use density was expressed as daily doses per 100 patient days (occupied bed days). For daily dose definition, both hospital adapted doses of antibiotics ("recommended daily dose", RDD) as well as the official WHO-defined daily doses (DDD) were used. RESULTS: The overall antibiotic use density was 43.5 RDD/100 patient days (median) with an interquartile range of 36-48 RDD/100 - corresponding to a median of 64.4 DDD/100 (interquartile range, 53-73 DDD/100). The antibiotic use levels in university hospitals were higher than in non-university hospitals that, in turn, showed similar antibiotic use density values across different hospital size categories. Antibiotic use density values for intensive care units were approximately twice as high as for normal wards but the proportion of antibiotic doses prescribed in intensive care per hospital-wide consumption was only 12â % (non-university hospitals) to 18â % (university hospitals). Extensive antibiotic use was also observed in university hospital hematology-oncology departments. Overall, cephalosporins were used slightly more frequently than penicillins, and fluoroquinolones were the third most frequently prescribed drug class. The proportion of first and second generation cephalosporins, and of third and fourth generation cephalosporins ranged between 5-37â % and between <â 1 to 29â % of all dispensed antibiotic doses across the hospitals, respectively. The top five used drugs were cefuroxime, piperacillin-tazobactam, ceftriaxon, metronidazole und ciprofloxacin. CONCLUSIONS: Prescribing of antibiotics on almost every second day of hospitalization was extensive and highly variable, and the frequent use of cephalosporins is noteworthy. It is possible that the development of resistance and the rate of Clostridium difficile infection is associated with the diverse antibiotic use intensity and preferences for prescribing of cephalosporins and fluoroquinolones. Continuous antibiotic use surveillance and evaluation of prescribing patterns in acute care with feedback and benchmarking will help optimizing antibiotic use and better assessing strategies to minimize resistance and Clostridium difficile infection, and eventually improve patient safety.
Assuntos
Antibacterianos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Benchmarking , Revisão de Uso de Medicamentos , Alemanha/epidemiologia , Melhoria de QualidadeRESUMO
Recent epidemiologic studies reveal both an increasing incidence and an escalation in resistance of invasive fungal infections in intensive care units. Primary therapy fails in 70 % of cases, depending on the underlying pathogens and diseases. The purpose of this review is to raise awareness for the topic of antifungal therapy failure, describe the clinical conditions in which it occurs, and suggest a possible algorithm for handling the situation of suspected primary therapy failure.
Assuntos
Antifúngicos/uso terapêutico , Cuidados Críticos/métodos , Micoses/tratamento farmacológico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Fúngica , Humanos , Unidades de Terapia Intensiva , Micoses/microbiologia , Sepse/tratamento farmacológico , Sepse/microbiologia , Falha de TratamentoRESUMO
WHAT IS KNOWN AND OBJECTIVES: Incorrect drug preparation for patients with feeding tubes can result in harm for the patient and the preparing person. Combined intervention programs are effective tools to reduce such preparation errors. However, to date, intervention programs have been mostly tested in hospitals with computerized physician order entry (CPOE), unit-dose systems, or ward-based clinical pharmacists. Hence, the primary objective of this study was to develop and evaluate an intervention program tailored to hospitals without such preconditions. METHODS: We conducted a prospective pre-/post-intervention study on a gastroenterological intensive care unit (ICU) and a surgical ward for oral, dental and maxillofacial diseases (surgical ward). During the study periods, observers documented and evaluated drug preparation processes of all peroral drugs for patients with feeding tubes. The primary endpoint was the rate of inappropriately crushed and/or suspended solid peroral drugs in regards to all solid peroral drugs. RESULTS AND DISCUSSION: Altogether, we evaluated 775 drug preparation processes of solid peroral drugs on the ICU and 975 on the surgical ward. The intervention program significantly reduced incorrect crushing and/or suspending of solid peroral drugs for administration to patients with feeding tubes from 9·8% to 4·2% (P < 0·01) on the ICU and from 5·7% to 1·4% (P < 0·01) on the surgical ward. WHAT IS NEW AND CONCLUSION: The implementation of the newly developed intervention program significantly reduced the rate of inappropriately prepared solid peroral drugs, suggesting that it is an effective measure to enable safe drug administration for inpatients with feeding tubes.
Assuntos
Química Farmacêutica/estatística & dados numéricos , Capacitação em Serviço/métodos , Intubação Gastrointestinal , Erros de Medicação/estatística & dados numéricos , Suspensões/química , Humanos , Recursos Humanos de Enfermagem Hospitalar , Estudos ProspectivosRESUMO
AIM: Presentation of a rare localization of bronchogenic cyst in retroperitoneum. MATERIAL: A case of a patient with retroperitoneal localization of a bronchogenic cyst with a prenatally diagnosed cystic formation. The surgery was indicated at the age of 6 owing to the progression of lesion. The histopathological examination of removed cyst revealed the diagnosis of bronchogenic cyst. For four years following the surgery, the patient was clinically free of complications. The regularly performed ultrasound examinations of the abdomen have been showing normal findings. CONCLUSION: Despite the fact that retroperitoneal localization of bronchial cyst is very rare it should be considered in differential diagnosis (Fig. 3, Ref. 16).
Assuntos
Cisto Broncogênico/diagnóstico , Cisto Broncogênico/cirurgia , Espaço Retroperitoneal , Ultrassonografia Pré-Natal , Cisto Broncogênico/diagnóstico por imagem , Criança , Diagnóstico Diferencial , Procedimentos Cirúrgicos do Sistema Digestório , Progressão da Doença , Feminino , Seguimentos , Humanos , Doenças Raras , Resultado do TratamentoRESUMO
Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were 51,517 in the IFD group and 30,454 in the control group. Incremental costs of 21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.
Assuntos
Custos de Cuidados de Saúde , Leucemia Mieloide Aguda/economia , Micoses/tratamento farmacológico , Micoses/economia , Síndromes Mielodisplásicas/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/economia , Antifúngicos/uso terapêutico , Feminino , Alemanha , Humanos , Tempo de Internação/economia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Estudos Retrospectivos , Adulto JovemRESUMO
Lung cancers are still divided into two major subgroups: small-cell and non-small cell lung cancer (NSCLC) irrespective of biological heterogeneity of NSCLC. It is a key task of the pathologist to provide an accurate classification of tumorous lesions to avoid the term NSCLC and to use it only in the vast minority of cases. Moreover, the most recent reclassification of pulmonary adenocarcinomas should be reflected in the standard biopsy protocol reporting. There is also an increasingly urgent need to provide high quality material for testing of the genetic characteristics of NSCLC, especially the presence and functional status of the EGFR receptor (epidermal growth factor receptor), as well as other potential prognostic markers. The requirement for the quality and swiftness of diagnosis puts major emphasis on the close multidisciplinary collaboration with the central role of a specialized pathologist, who coordinates the differential-diagnostic procedure. This in turn implies the necessity of accounting for the increasing financial burden of diagnostic departments.
Assuntos
Adenocarcinoma/classificação , Carcinoma Pulmonar de Células não Pequenas/classificação , Neoplasias Pulmonares/classificação , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , PrognósticoRESUMO
BACKGROUND: The aims of this prospective study were to determine the prevalence of clinically silent rejection changes and of nephrotoxicity of calcineurin inhibitors among repeated protocol biopsies of transplanted kidneys and to assess their impacts on chronic graft function and damage at the end of 1 year. METHODS: We performed 424 protocol biopsies among 158 patients over the first year after transplantation. We monitored parameters of graft function and progression of chronic changes among subjects with clinically silent rejection or toxicity for comparison with a control cohort showing normal histological findings. The results of statistical tests were considered to be significant at a level of P < .05. RESULTS: At 3 weeks, 3 months, and 12 months, there were normal histological findings among 30 (19%), 21 (14.8%), and 14 (11.3%) patients, respectively; subclinical rejection changes occurred in 49 (31%), 36 (25.4%), and 20 (16.2%) grafts, respectively. At the third week, histological signs of toxicity occurred in 33 (20.9%) patients with significant persistence despite reductions in calcineurin inhibitor doses. At the end of 1 year of follow-up, both subclinical and toxic changes produced similar increases in chronic changes as quantified by the Banff score and were significantly different from the control group (P < .05). Serum creatinine concentrations and glomerular filtration rates did not accurately reflect the degree of graft damage in the early posttransplantation period. CONCLUSIONS: Subclinical rejection and toxic changes among a significant proportion of grafts are associated with progression of chronic changes already over the first year following transplantation. Hence they represent independent risk factors for the development of irreversible graft damage. Protocol biopsy seems to be an important method to monitor immunosuppressive therapy.
Assuntos
Protocolos Clínicos , Monitoramento de Medicamentos , Imunossupressores/uso terapêutico , Transplante de Rim , Adolescente , Adulto , Idoso , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor ß, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
Assuntos
Sarcoidose Pulmonar/metabolismo , Proteínas com Domínio T/metabolismo , Células Th1/metabolismo , Regulação para Cima , Adulto , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Feminino , Expressão Gênica , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Pulmão/metabolismo , Linfonodos/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Receptores CXCR6 , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/metabolismo , Receptores Virais/genética , Receptores Virais/metabolismo , Sarcoidose Pulmonar/genética , Sarcoidose Pulmonar/imunologia , Células Th1/imunologiaRESUMO
Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin inspection in high-risk immunocompromised patients must be stressed and suitable therapy must be indicated in suspected lesions.