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1.
BMC Infect Dis ; 21(1): 521, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078297

RESUMO

BACKGROUND: The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus (HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times. CASE PRESENTATION: In 2020, a 52-year old HIV-positive bisexual male patient was admitted to our department with a 4-month history of moderately itchy cutaneous lesions localized at his neck, trunk and arms. In 2013, the patient presented with a classic syphilitic roseola of the trunk and a secondary syphilis was diagnosed, with increased levels of rapid plasma reagin (RPR), Treponema pallidum hemagglutination assay (TPHA), anti-Treponema pallidum IgM and IgG Index. A second episode occurred in 2018, as a primary syphilis with multiple ulcerative lesions of the penis, and increased levels of RPR, IgG and IgM. In 2019, a further episode of secondary syphilis was treated with Doxycycline. In 2020, erythematous and papular lesions with vesicular components and urticarial erythema multiforme (EM)-like lesions were present at the neck, trunk and arms. Serological tests and Nucleic Acid Amplification Test (NAAT) for Treponema Pallidum were performed, as well as a cutaneous biopsy with histological and immunohistochemical evaluation of one lesion. NAAT was negative for T. pallidum. Serological test results were discordant with a new syphilis infection, showing only increased levels of RPR and anti-Treponema IgG. The cutaneous biopsy revealed a non specific histological pattern, while the immunohistochemical evaluation with anti-spirochetal antibodies was mandatory for the diagnosis of recent syphilis, showing clusters of rod-shaped elements, some of which with spiral form, focally present at the epidermis and adnexal structures. CONCLUSIONS: Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.


Assuntos
Sífilis/diagnóstico , Treponema pallidum/isolamento & purificação , Anticorpos Antibacterianos/sangue , Biópsia , Infecções por HIV/complicações , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva , Minorias Sexuais e de Gênero , Sífilis/patologia , Sorodiagnóstico da Sífilis , Treponema pallidum/imunologia
2.
Nat Commun ; 12(1): 3386, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099644

RESUMO

During early pregnancy in the mouse, nidatory estrogen (E2) stimulates endometrial receptivity by activating a network of signaling pathways that is not yet fully characterized. Here, we report that bone morphogenetic proteins (BMPs) control endometrial receptivity via a conserved activin receptor type 2 A (ACVR2A) and SMAD1/5 signaling pathway. Mice were generated to contain single or double conditional deletion of SMAD1/5 and ACVR2A/ACVR2B receptors using progesterone receptor (PR)-cre. Female mice with SMAD1/5 deletion display endometrial defects that result in the development of cystic endometrial glands, a hyperproliferative endometrial epithelium during the window of implantation, and impaired apicobasal transformation that prevents embryo implantation and leads to infertility. Analysis of Acvr2a-PRcre and Acvr2b-PRcre pregnant mice determined that BMP signaling occurs via ACVR2A and that ACVR2B is dispensable during embryo implantation. Therefore, BMPs signal through a conserved endometrial ACVR2A/SMAD1/5 pathway that promotes endometrial receptivity during embryo implantation.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Implantação do Embrião , Infertilidade Feminina/genética , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Animais , Biópsia , Modelos Animais de Doenças , Endométrio/metabolismo , Endométrio/patologia , Estrogênios/metabolismo , Feminino , Humanos , Camundongos , Camundongos Knockout , Gravidez , Transdução de Sinais/fisiologia , Proteína Smad1/análise , Proteína Smad1/genética , Proteína Smad1/metabolismo , Proteína Smad5/análise , Proteína Smad5/genética , Proteína Smad5/metabolismo
3.
J Pak Med Assoc ; 71(6): 1701-1702, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34111104

RESUMO

Abdominal wall sarcoma belongs to a heterogeneous group of uncommon malignant neoplastic conditions with differentiated morphological patterns and originating from mesenchymal tissues. Soft tissue sarcomas predominantly involve the lower and upper limbs and retroperitoneum. We present a case of a 30-year-old patient, complaining of swelling in the left flank whose magnetic resonance imaging (MRI) revealed a solid tumour on the abdominal wall of the flank and biopsy turned out to be synovial sarcoma.


Assuntos
Parede Abdominal , Sarcoma Sinovial , Parede Abdominal/diagnóstico por imagem , Adulto , Biópsia , Humanos , Imageamento por Ressonância Magnética , Sarcoma Sinovial/diagnóstico por imagem
4.
BMJ Case Rep ; 14(5)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059537

RESUMO

A 35-year-old woman presented with a constellation of systemic symptoms: rashes, weight loss, arthralgia and mouth ulcers. Six months afterwards, she experienced bilateral and sequential reduction in vision, and was found to have bilateral vaso-occlusive retinopathy, with critical macular ischaemia in the left eye. Her serological markers were consistent with a diagnosis of lupus. A lymph node biopsy confirmed Kikuchi-Fujimoto disease, a benign condition of unknown cause characterised by fever, cervical and axillary lymphadenopathy. Given that this overlap syndrome was associated with a number of systemic features and had affected the eyes, an immunosuppressive regime with rituximab was considered prudent. This rendered her vasculitis stable and non-progressive, and there were signs of partial retinal microvasculature recovery on optical coherence tomography angiography. There is increasing evidence of an overlap between Kikuchi-Fujimoto disease and systemic lupus erythematosus, which is associated with vaso-occlusive retinopathy. In these instances, a multidisciplinary approach is warranted, with consideration of appropriate treatment in order to prevent harmful sequelae of vasculitis. Our treatment with rituximab abated the disease process, although close follow-up is paramount to monitor results and side-effects of treatment.


Assuntos
Linfadenite Histiocítica Necrosante , Lúpus Eritematoso Sistêmico , Doenças Retinianas , Adulto , Biópsia , Feminino , Febre , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/complicações
5.
Med Intensiva (Engl Ed) ; 45(5): 261-270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34059216

RESUMO

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. OBJECTIVE: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. DESIGN: A prospective cohort study was carried out. SETTING: Intensive Care Unit of a tertiary hospital. PATIENTS: The first 22 consecutive COVID-19 deaths. MEASUREMENTS: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. RESULTS: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. LIMITATION: Limited sample size. CONCLUSIONS: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.


Assuntos
COVID-19/patologia , Pulmão/patologia , Síndrome do Desconforto Respiratório/patologia , Idoso , Linfócitos B , Biópsia , COVID-19/complicações , Feminino , Humanos , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/isolamento & purificação , Linfócitos T , Centros de Atenção Terciária , Fatores de Tempo
6.
Cells ; 10(5)2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064487

RESUMO

Liver injury in COVID-19 patients has progressively emerged, even in those without a history of liver disease, yet the mechanism of liver pathogenicity is still controversial. COVID-19 is frequently associated with increased serum ferritin levels, and hyperferritinemia was shown to correlate with illness severity. The liver is the major site for iron storage, and conditions of iron overload have been established to have a pathogenic role in development of liver diseases. We presented here six patients who developed severe COVID-19, with biochemical evidence of liver failure. Three cases were survived patients, who underwent liver biopsy; the other three were deceased patients, who were autopsied. None of the patients suffered underlying liver pathologies. Histopathological and ultrastructural analyses were performed. The most striking finding we demonstrated in all patients was iron accumulation into hepatocytes, associated with degenerative changes. Abundant ferritin particles were found enclosed in siderosomes, and large aggregates of hemosiderin were found, often in close contact with damaged mitochondria. Iron-caused oxidative stress may be responsible for mitochondria metabolic dysfunction. In agreement with this, association between mitochondria and lipid droplets was also found. Overall, our data suggest that hepatic iron overload could be the pathogenic trigger of liver injury associated to COVID-19.


Assuntos
COVID-19/diagnóstico , Sobrecarga de Ferro/etiologia , Falência Hepática/etiologia , Fígado/patologia , Índice de Gravidade de Doença , Adulto , Idoso , Antivirais , Biópsia , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Feminino , Ferritinas/análise , Hepatócitos/citologia , Hepatócitos/patologia , Humanos , Ferro/análise , Ferro/metabolismo , Sobrecarga de Ferro/mortalidade , Sobrecarga de Ferro/patologia , Sobrecarga de Ferro/terapia , Fígado/citologia , Fígado/metabolismo , Falência Hepática/mortalidade , Falência Hepática/patologia , Falência Hepática/terapia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Mitocôndrias/patologia , Respiração com Pressão Positiva , SARS-CoV-2/isolamento & purificação
7.
Rev Med Chil ; 149(1): 7-12, 2021 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-34106130

RESUMO

BACKGROUND: The discovery of the phospholipase A2 receptor antigen and its highly specific autoantibody (anti-PLA2R Ab) was useful for the diagnosis and follow-up of patients with membranous nephropathy (MN). Thus, some international guidelines recommend not performing renal biopsy in patients with positive serum anti-PLA2R Ab. AIM: To evaluate the prevalence of anti-PLA2R Ab in serum and renal tissue samples from Chilean patients with primary MN. MATERIAL AND METHODS: Twenty-eight patients aged 50 ± 14 years (20 males) with biopsy-proven primary MN plus a negative workup for secondary causes were included. Measurements of serum and renal histologic anti-PLA2R Ab were performed. The relationship between the findings of serum and tissue anti-PLA2R Ab was evaluated. RESULTS: Fifteen patients (54 %) had anti-PLA2R Ab presence in serum and 19 patients (68%) had positive anti-PLA2R Ab in the renal biopsy. All patients with positive serum anti-PLA2R Ab had positive antibodies on immunohistochemistry. CONCLUSIONS: Serum anti-PLA2R Ab is potentially useful in the diagnosis of patients with suspected primary MN in Chilean population.


Assuntos
Glomerulonefrite Membranosa , Receptores da Fosfolipase A2 , Autoanticorpos , Biópsia , Chile , Humanos , Rim , Masculino
8.
Ann Palliat Med ; 10(5): 5509-5519, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34107703

RESUMO

BACKGROUND: In consideration of the limitations of liver biopsy, the past years have seen a great advance in the application of noninvasive indices in assessing liver fibrosis. However, the accuracies of the existing indices to determine liver fibrosis in patients with chronic hepatitis B (CHB) are still unsatisfactory. Here, we established a noninvasive diagnostic model for assessing significant liver fibrosis (SLF) in CHB patients based on serum chitinase 3-like 1 (CH3L1) and routine clinical indicators. METHODS: The clinical data of 337 CHB patients treated at Xiamen Hospital of Traditional Chinese Medicine from December 1, 2019, to September 30, 2020, were collected in this cross-sectional study. All the enrolled cases were randomly divided into a training cohort (n=270) and a validation cohort (n=67). The training cohort was further divided into a non-significant liver fibrosis (NSLF) group (stages S0-S1; n=189; used as the control group) and an SLF group (stage S2-S4; n=81) based on the Scheuer scoring system. Univariate and multivariate logistic regression analyses were performed to screen for independent predictors of SLF in CHB patients and to establish a diagnostic model. RESULTS: The results of univariate and multivariate logistic regression analysis showed that CHI3L1, AFP and PLT were independent predictors of SLF in CHB patients, and the diagnostic model was established as follows: CHI3L1/AFP/PLT (CAP) = 0.600 × CHI3L1/upper limit of normal (ULN) + 0.252 × AFP/ULN - 1.424 × PLT/lower limit of normal (LLN) - 1.223. The area under the receiver operating characteristic (AUROC) of this model for the diagnosis of SLF in the training cohort and the validation cohort was 0.805 and 0.819, respectively, showing no statistically significant difference (P>0.05), and the AUROC for the diagnosis of SLF in the whole cohort was significantly higher than those of other noninvasive markers including aspartate transaminase to platelet ratio index (APRI), fibrosis 4 score (FIB-4) and CHI3L1 (all P<0.05). CONCLUSIONS: The newly established model has a good diagnostic efficacy for SLF in CHB patients and is superior to other noninvasive markers including APRI, FIB-4, and CHI3L1. Thus, it can be used as a noninvasive diagnostic index for liver fibrosis in CHB patients.


Assuntos
Hepatite B Crônica , Aspartato Aminotransferases , Biomarcadores , Biópsia , Proteína 1 Semelhante à Quitinase-3 , Estudos Transversais , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Humanos , Fígado , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
BMJ Case Rep ; 14(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108156

RESUMO

We present a case of a 70-year-old Caucasian woman with multisystem granulomatous disease involving her lungs, bones and lymph nodes. The patient initially presented with cervical lymphadenopathy and subsequently developed progressive breathlessness. Imaging revealed extensive mediastinal, hilar and intra-abdominal lymphadenopathy as well as bilateral pulmonary parenchymal infiltrates. Lymph node and lung biopsy confirmed non-necrotising granulomatous inflammation while a BAL showed scanty growth of Cryptococcus neoformans and moderate growth of Staphylococcus aureus The patient received intravenous ceftriaxone and had a good response to treatment. She also completed 3 months of oral fluconazole. Although a diagnosis of sarcoidosis was considered most likely, the patient was not initially started on systemic corticosteroids due to concern around possible infection and initial response to antimicrobials. However, her exercise tolerance gradually deteriorated. A craniofacial CT revealed multiple lytic lesions involving the skull and visualised cervical spine. Biopsy of a clivus lesion revealed non-necrotising granulomatous inflammation while fungal cultures and histopathological stains were negative. The patient was diagnosed with widespread sarcoidosis and she was initiated on prednisolone and methotrexate which led to marked clinical and radiological improvement.


Assuntos
Linfadenopatia , Sarcoidose , Idoso , Biópsia , Feminino , Granuloma/diagnóstico por imagem , Granuloma/tratamento farmacológico , Humanos , Pulmão , Sarcoidose/diagnóstico , Sarcoidose/diagnóstico por imagem
10.
BMJ Case Rep ; 14(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34078622

RESUMO

We describe a 65-year-old man who during his service in the military developed an acute onset of burning pain in his feet and hands shortly after an acute, severe exposure to the fumes of chemical agent resistant coating (CARC). This chemical is used in the military to paint vehicles and equipment to create metal surfaces resistant to corrosion and penetration by chemical agents. Extensive laboratory workup for peripheral neuropathies was unremarkable. Nerve conduction studies showed axonal-loss polyneuropathy. Skin biopsy confirmed a small-fibre polyneuropathy (SFP). His burning pain persisted over three decades and was partially controlled with tramadol. This is the first case of SFP caused by acute CARC exposure with long-term surveillance.


Assuntos
Doenças do Sistema Nervoso Periférico , Polineuropatias , Idoso , Biópsia , Humanos , Masculino , Condução Nervosa , Exame Neurológico , Dor , Polineuropatias/induzido quimicamente , Polineuropatias/diagnóstico , Polineuropatias/tratamento farmacológico
11.
Arch Esp Urol ; 74(5): 477-487, 2021 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-34080567

RESUMO

OBJECTIVE: VA is currently considered the treatment of choice for patients with low and very low risk prostate cancer. We analyzed the evolution of this treatment strategy in our series and adherence to the protocol. MATERIAL AND METHODS: Ambispective study of patients in VA in our center between 2014- 2019. 237 meet inclusion criteria, of which 142 (60%) have a minimum of 12 months of follow- up. Mean age: 68.5 (4678), median PSA 6.37 ng / ml (1-33). 229 (96.6%) are ISUP 1 and 8 (3.4%) ISUP 2. Objectives are proposed to assess our adherence to the protocol. Descriptive statistics are used to communicate the results. RESULTS: According to the classification by risk groups of the NCCN, 145 (61.2%), 49 (20.7%) and 42 (17.7%) were very low risk, low risk and favorable intermediate risk patients, respectively. The median of follow-up is 14 months (0-66). Of the patients with a minimum follow-up of 12 months, 107 (75.4%) were re-biopsied. 80 (33.8%) leave the protocol in these 5 years, 31.3% (25) by their own decision, 55% (44) due to medical criteria, and 11.3% (9) go to WW. After 5 years of follow-up, 99.2% of patients are still alive, 0.8% died of specific non-cancer causes. Of the objectives to assess adherence, 8 are achieved, 1 partially and 1 is not evaluable. CONCLUSIONS: VA in our center is already the treatment of choice for very low-risk patients, with a constant increase from year to year. Adherence to the protocol has been favorable during the period of time studied.


Assuntos
Neoplasias da Próstata , Conduta Expectante , Idoso , Biópsia , Humanos , Masculino , Antígeno Prostático Específico , Fatores de Risco
12.
BMC Gastroenterol ; 21(1): 250, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34092231

RESUMO

BACKGROUND: Few studies have reported whether a biopsy in emergency gastroscopy (EG) increased the risk of rebleeding in patients with Forrest I acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) combined with suspected malignant gastric ulcer (SMGU). This study aims to conduct a multicenter retrospective cohort study using propensity score matching to verify whether a biopsy in EG increases the risk of rebleeding in patients diagnosed with Forrest I ANVUGIB combined with SMGU. METHODS: Using the data for propensity-matched patients, logistic regression models were fitted using rebleeding as the dependent variable. Survival time was defined as the length of time the patient experienced from visiting the emergency department to rebleeding. We used the Kaplan-Meier (KM) method to analyze the 30-day survival of the patients with and without a biopsy after matching, and the log-rank test was performed to examine the differences in survival. RESULTS: With the use of propensity score matching, 308 patients who underwent a biopsy in EG were matched with 308 patients who did not. In the five logistic regression models, there were no significant group differences in the risk of rebleeding in patients with Forrest I ANVUGIB combined with SMGU between the biopsy and no-biopsy groups. The probability of survival was not significantly different between the no-biopsy and biopsy groups. CONCLUSIONS: In this multicenter, retrospective propensity score matching cohort study, compared with patients without a biopsy, patients with a biopsy during EG had no increased risk of rebleeding, and there was no significant difference in the rate of rebleeding.


Assuntos
Úlcera Gástrica , Biópsia , Estudos de Coortes , Serviço Hospitalar de Emergência , Hemorragia Gastrointestinal/etiologia , Gastroscopia , Humanos , Recidiva , Estudos Retrospectivos , Úlcera Gástrica/complicações
13.
World J Gastroenterol ; 27(20): 2603-2614, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34092978

RESUMO

BACKGROUND: Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease. AIM: To understand patterns of follow-up and management of patients with celiac disease, and to characterize symptoms and villous atrophy after diagnosis. METHODS: A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease. Three gastroenterology referral centers, with substantial expertise in celiac disease, participated in the United Kingdom, United States, and Norway. Demographic and clinical data were collected from medical charts. Descriptive analyses were conducted on patients with biopsy-confirmed celiac disease, diagnosed between 2008 and 2012, with at least one follow-up visit before December 31, 2017. Patient demographic and clinical characteristics, biopsy/serology tests and results, symptoms, and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period (i.e., before the study end date of December 31, 2017). RESULTS: A total of 300 patients were included in this study [72% female; mean age at diagnosis: 38.9 years, standard deviation (SD) 17.2]. Patients were followed-up for a mean of 29.9 mo (SD 22.1) and there were, on average, three follow-up visits per patient during the study period. Over two-thirds (68.4%) of patients were recorded as having ongoing gastrointestinal symptoms and 11.0% had ongoing symptoms and enteropathy during follow-up. Approximately 80% of patients were referred to a dietician at least once during the follow-up period. Half (50.0%) of the patients underwent at least one follow-up duodenal biopsy and 36.6% had continued villous atrophy. Patterns of monitoring varied between sites. Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration. CONCLUSION: This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.


Assuntos
Doença Celíaca , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Feminino , Humanos , Masculino , Noruega , Estudos Retrospectivos , Reino Unido , Estados Unidos
14.
Med Clin North Am ; 105(4): 643-661, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059243

RESUMO

Melanoma accounts for approximately 1% of all skin cancers but contributes to almost all skin cancer deaths. The developing picture suggests that melanoma phenotypes are driven by epigenetic mechanisms that reflect a complex interplay between genotype and environment. Furthermore, the growing consensus is that current classification standards, notwithstanding pertinent clinical history and appropriate biopsy, fall short of capturing the vast complexity of the disease. This article summarizes the current understanding of the clinical picture of melanoma, with a focus on the tremendous breakthroughs in molecular classification and therapeutics.


Assuntos
Melanoma/diagnóstico , Melanoma/genética , Estadiamento de Neoplasias/métodos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso , Biópsia , Tratamento Farmacológico/métodos , Epigênese Genética/genética , Feminino , GTP Fosfo-Hidrolases/antagonistas & inibidores , Genótipo , Humanos , Imunoterapia/métodos , Incidência , Masculino , Melanoma/epidemiologia , Melanoma/terapia , Proteínas de Membrana/antagonistas & inibidores , Cirurgia de Mohs/métodos , Terapia de Alvo Molecular/métodos , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/mortalidade , Estados Unidos/epidemiologia , Adulto Jovem
15.
Nat Commun ; 12(1): 2716, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976135

RESUMO

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano , Granuloma/patologia , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/patologia , Antituberculosos/uso terapêutico , Biópsia , Células Clonais , Estudos de Coortes , Variação Genética , República da Geórgia , Granuloma/tratamento farmacológico , Granuloma/microbiologia , Granuloma/cirurgia , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pulmão/cirurgia , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Espécies Reativas de Oxigênio/metabolismo , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/cirurgia
16.
Medicine (Baltimore) ; 100(21): e25861, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032698

RESUMO

RATIONALE: Gastric adenocarcinoma of fundic gland (chief cell predominant type) (GA-FG-CCP) is a new, rare variant of gastric adenocarcinoma, which is characterized by mild nuclear atypia and specific immunohistochemical markers. PATIENT CONCERNS: An 84-year-old Chinese man was referred to our hospital for endoscopic resection of a gastric lesion. INTERVENTIONS: We performed endoscopic submucosal dissection, and successfully removed the lesion. DIAGNOSIS: Esophago gastroduodenoscopy showed a slightly elevated lesion with a diameter of 22 mm in the posterior wall of cardia. Magnifying endoscopy with narrow band imaging revealed an abnormal microsurface and microvessels on the tumor surface. Endoscopic ultrasonography revealed a hypoechoic mass located in the first layer. The pathological diagnosis of the biopsy specimens indicated that the tumor was high grade intraepithelial neoplasia. The pathological diagnosis differed between the superficial and deeper part of the lesion. The superficial part was composed of a tubular structure with prominent atypia and was diagnosed as well differentiated intestinal adenocarcinoma. The deeper part was composed of a well-differentiated tubular adenocarcinoma mimicking the fundic gland cells, mainly the chief cells. The tumor cells showed mild nuclear atypia and was positive for pepsinogen-I (PG-I) and mucin-6 (MUC6). This deeper part was diagnosed as GA-FG-CCP. OUTCOMES: The tumor was successfully removed. This patient had no discomfort during the follow-up period (10 months). LESSONS: We present a rare case of GA-FG-CCP coexisted with well-differentiated tubular adenocarcinoma. GA-FG-CCP exists in the deep mucosal layer and the muscularis mucosa, which could not be found under endoscopy, but could be discerned in pathology with mild nuclear atypia and special biomarkers.


Assuntos
Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma/diagnóstico , Fundo Gástrico/patologia , Neoplasias Complexas Mistas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/cirurgia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Celulas Principais Gástricas/patologia , Endoscopia do Sistema Digestório , Endossonografia , Gastrectomia , Fundo Gástrico/citologia , Fundo Gástrico/diagnóstico por imagem , Fundo Gástrico/cirurgia , Humanos , Mucosa Intestinal/patologia , Masculino , Mucina-6/análise , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/cirurgia , Pepsinogênio A/análise , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
17.
Medicine (Baltimore) ; 100(21): e25985, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032713

RESUMO

ABSTRACT: Cytopenias in systemic lupus erythematosus (SLE) require clinical and laboratory workup and bone marrow (BM) examination to determine the cause and for appropriate patient management. Common causes include an increase in SLE activity, immune-mediated hemolysis, iron deficiency, antiphospholipid antibody syndrome, infection, or the effect of medications. We retrospectively evaluated the clinical and laboratory findings of patients with SLE and cytopenias who had undergone BM studies to determine the indicators of malignancy.We retrospectively reviewed medical records of patients with SLE who presented with cytopenias for their disease course, medications, laboratory parameters and documented the spectrum of morphological changes in BM including CD34 expression.Twenty patients with SLE had undergone BM biopsy for evaluation of cytopenias. 14/20 (70%) of the patients had reactive BM, and the rest had hematologic malignancies involving the BM. Of these 14 patients, 8 had hypocellular marrow with loss of precursor cells (low CD34), 4 had left shift in myeloid lineage, 3 had serous atrophy, and 1had multilineage dysplasia. The 6 patients with hematologic malignancies included 2 with diffuse large B cell lymphoma, and one each of natural killer/T cell lymphoma, post-transplant lymphoproliferative disorder, Hodgkin lymphoma, and myelodysplastic syndrome evolving to acute myelogenous leukemia. The presence of autoantibodies, SLE activity, and lupus nephritis were comparable in patients with and without neoplasia. However, the duration of the use of multiple immunosuppressants, years since renal transplant (22 vs 10), multiple transplants, and the presence of other autoimmune diseases were greater in those with neoplasia. Two of the 14 patients with non-neoplastic BM and 1 with the neoplastic BM had nonhematological malignancy.Clinical and laboratory findings, the number of transplants, and the use of immunosuppressive agents can guide physicians to identify patients with a higher risk of developing hematologic malignancy. BM findings of cytopenia in SLE are often due to increased disease activity causing global cell death and dysmaturation. SLE patients presenting with cytopenias, with a history of long-term exposure to immunosuppressive drugs, should be regularly screened for hematologic and nonhematologic malignancies.


Assuntos
Neoplasias Hematológicas/epidemiologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Leucopenia/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Trombocitopenia/diagnóstico , Adulto , Idoso , Biópsia/estatística & dados numéricos , Medula Óssea/patologia , Exame de Medula Óssea/estatística & dados numéricos , Suscetibilidade a Doenças , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Humanos , Transplante de Rim/estatística & dados numéricos , Leucopenia/sangue , Leucopenia/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/imunologia , Adulto Jovem
19.
Anticancer Res ; 41(5): 2217-2225, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952448

RESUMO

BACKGROUND/AIM: Although surgical thoracoscopy is recommended in the diagnosis of malignant pleural mesothelioma (MPM), the invasiveness of this procedure is of strong concern. Our review aimed to evaluate the accuracies of medical thoracoscopy (MT), computed tomography (CT)-guided biopsy, and ultrasound (US)-guided biopsy in the diagnosis of MPM among patients with pleural effusion. MATERIALS AND METHODS: We searched the MEDLINE, Embase, Central, and International Clinical Trials Registry Platform databases for studies evaluating the diagnostic accuracy of at least one of the biopsy procedures among patients with pleural effusion of unknown aetiology who had undergone thoracentesis and/or blind biopsy. A hierarchical summary receiver operating curve was created for MT. RESULTS: Following full-text screening, 15 studies were included. MT studies had a high risk of bias and low applicability concern; however, hierarchical summary receiver operating curve revealed that MT had a high sensitivity. CONCLUSION: MT might be a useful rule-in test for guiding the use of more invasive diagnostic procedures.


Assuntos
Biópsia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pleurais/patologia , Toracoscopia/métodos , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Humanos , Neoplasias Pleurais/diagnóstico , Curva ROC , Reprodutibilidade dos Testes
20.
Medicine (Baltimore) ; 100(18): e25845, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950999

RESUMO

ABSTRACT: We examined the association between diuretic administration before the diagnosis of minimal change disease and the incidence of acute kidney injury. Moreover, we examined whether the use of diuretics affected the time to complete remission in adults with such disease.The present study was a single-center, retrospective, observational cohort study. We included 107 patients with biopsy-proven minimal change disease who were treated at a tertiary referral center in Japan between January 1, 2000 and March 31, 2019. All biopsy specimens were examined by a board-certified renal pathologist. The patients were considered to have minimal change disease when the kidney biopsy specimen had no glomerular lesions or only mild focal mesangial prominence (not exceeding 3 or 4 cells per segment) by light microscopy and/or foot process effacement by electron microscopy. Logistic regression and Kaplan-Meier curve analyses were performed, comparing the data of patients who received diuretics or not.The median age was 47 (28-66) years, 52% of patients were women, and the median proteinuria dosage was 8.3 (5.3-11.2) g/d. When minimal change disease was diagnosed, 27% of patients were taking diuretics. Within 30 days after the diagnosis, acute kidney injury occurred in 27% of patients. On multivariable logistic regression analysis, the use of diuretics was significantly associated with a higher risk of acute kidney injury. The use of diuretics was also associated with a longer time to complete remission.Diuretic administration can be associated with an elevated acute kidney injury risk and longer remission time in adult patients with newly diagnosed minimal change disease.


Assuntos
Injúria Renal Aguda/epidemiologia , Diuréticos/efeitos adversos , Edema/tratamento farmacológico , Nefrose Lipoide/diagnóstico , Injúria Renal Aguda/etiologia , Adulto , Idoso , Biópsia , Diuréticos/administração & dosagem , Edema/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Néfrons/efeitos dos fármacos , Néfrons/patologia , Nefrose Lipoide/complicações , Nefrose Lipoide/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
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