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1.
Am J Hematol ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419248

RESUMO

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50 years who had off-site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off-site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off-site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co-factor (VWF:RCo), 122 (55%) were low off-site and 71 (32%) were low onsite; similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off-site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off-site processing compared to onsite (McNemar's test p-value < 0.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist. This article is protected by copyright. All rights reserved.

2.
J Cancer Surviv ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32394044

RESUMO

PURPOSE: To create a community of learning involving primary care providers and subspecialist to enhance providers' knowledge regarding care of adult childhood cancer survivors (CCS). METHODS: A stepwise approach was used to develop educational opportunities for providers. This process started with a local/regional in-person conference, which informed a webinar series, and resulted in the development of enduring material using a dynamic learning management system. RESULTS: Participants in all three learning platforms had an increase in knowledge from baseline regarding care for adult CCS. Majority of participants at the in-person conference and webinar series were oncology or other specialty providers. The enduring dynamic learning management system successfully reached a variety of providers and other allied health providers across the country. There was a slightly higher rate of participation on this platform by primary care providers of 12.5%. CONCLUSIONS: Care providers' knowledge of survivorship needs of adult CCS can be increased by multiple forms of instruction. However, the dynamic learning management system was most successful at reaching a broad audience. Advertisement through local and national organizations was not as successful as anticipated. Additional strategies are needed to successfully engage providers, specifically primary care providers (PCPs). IMPLICATIONS FOR CANCER SURVIVORS: The professional development needs of primary care providers regarding care of adult CCS is well recognized. A dynamic learning management system may represent the most convenient and accessible way to provide education, but new strategies for increasing providers' awareness and engagement are required. The goal of improving care of adult CCS requires increased providers knowledge.

3.
Med Biol Eng Comput ; 58(5): 1127-1146, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32189205

RESUMO

The automatic cell analysis method is capable of segmenting the cells and can detect the number of live/dead cells present in the body. This study proposed a novel non-linear segmentation model (NSM) for the segmentation and quantification of live/dead cells present in the body. This work also reveals the aspects of electromagnetic radiation on the cell body. The bright images of the hippocampal CA3 region of the rat brain under the resolution of 60 × objective are used to analyze the effects called NISSL-stained dataset. The proposed non-linear segmentation model segments the foreground cells from the cell images based on the linear regression analysis. These foreground cells further get discriminated as live/dead cells and quantified using shape descriptors and geometric method, respectively. The proposed segmentation model is showing promising results (accuracy, 82.82%) in comparison with the existing renowned approaches. The counting analysis of live and dead cells using the proposed method is far better than the manual counts. Therefore, the proposed segmentation model and quantifying procedure is an amalgamated method for cell quantification that yields better segmentation results and provides pithy insights into the analysis of neuronal anomalies at a microscopic level. Graphical Abstract Resultant View of the overall proposed approach.

5.
Glob Public Health ; 15(6): 889-904, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32070217

RESUMO

To inform PrEP roll out, Ashodaya Samithi, a sex workers' collective, conducted a community-led prospective demonstration project among female sex workers in Mysore and Mandya, India. Following a community preparedness phase and pre-screening, participants were recruited for clinical screening and enrolment, provided PrEP as part of combination HIV prevention, and followed for 16 months. Adherence was measured by self-reported pill intake and by tenofovir blood level testing among a subset of participants. Of the 647 participants enrolled, 640 completed follow-up. Condom use remained stable and no HIV seroconversions occurred. Self-reported daily PrEP intake over the last month was 97.97% at the end of the study. Tenofovir blood levels >40 ng/mL (consistent with steady state dosing) were detected among 80% (n = 68/85) and 90.48% (n = 76/84) of participants at month 3 and 6, respectively. Our study holds important insights for rolling out PrEP in community settings as part of targeted HIV prevention interventions.

6.
Am J Hematol ; 95(5): 472-482, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32043619

RESUMO

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.

7.
PLoS One ; 15(2): e0228132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017775

RESUMO

BACKGROUND: Oral cancer is one of the most common diseases globally. Conventional oral examination and histopathological examination are the two main clinical methods for diagnosing oral cancer early. VELscope is an oral cancer-screening device that exploited autofluorescence. It yields inconsistent results when used to differentiate between normal, premalignant and malignant lesions. We develop a new method to increase the accuracy of differentiation. MATERIALS AND METHODS: Five samples (images) of each of 21 normal mucosae, as well as 31 premalignant and 16 malignant lesions of the tongue and buccal mucosa were collected under both white light and autofluorescence (VELscope, 400-460 nm wavelength). The images were developed using an iPod (Apple, Atlanta Georgia, USA). RESULTS: The normalized intensity and standard deviation of intensity were calculated to classify image pixels from the region of interest (ROI). Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) classifiers were used. The performance of both of the classifiers was evaluated with respect to accuracy, precision, and recall. These parameters were used for multiclass classification. The accuracy rate of LDA with un-normalized data was increased by 2% and 14% and that of QDA was increased by 16% and 25% for the tongue and buccal mucosa, respectively. CONCLUSION: The QDA algorithm outperforms the LDA classifier in the analysis of autofluorescence images with respect to all of the standard evaluation parameters.


Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias Bucais/diagnóstico por imagem , Imagem Óptica , Adulto , Análise Discriminante , Feminino , Humanos , Masculino , Mucosa Bucal/diagnóstico por imagem
8.
J Clin Tuberc Other Mycobact Dis ; 17: 100124, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788566

RESUMO

Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis. It is known to be the second-largest cause of death and models a severe risk to public health throughout the world. Though it affects people of almost every age, individuals with weakened immune systems, (e.g., HIV infection) are more likely to get infected. The present study deals with analyzing non-synonymous mutations in anti-tuberculosis drugs, which may have a significant role in causing XDR and MDR tuberculosis drug resistance. Continued use of tuberculosis drugs, discontinuation of medicines and various other factors can promote drug resistance in the host's body. To understand the actual cause of resistance, we have identified some patterns of mutations which might be responsible for a change in the structure of the protein, ultimately causing drug resistance. Here, we aim to present some of the unique mutation patterns in the genes associated with the marketed drugs that might have a deleterious effect. In this study, we have used molecular docking approach for understanding the ligand binding affinity of the mutated drugs. The results are further validated by molecular dynamics studies.

9.
J Food Biochem ; 43(9): e12971, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489671

RESUMO

The aim of this study was to evaluate in vitro antifungal potential of carrot seed extracts, its essential oil, different fractions, isolated compounds, and their derivatives against three phytopathogenic rice fungi (Fusarium moniliforme, Bipolaris oryzae, and Rhizoctonia solani) using poisoned food technique. Carrot seed essential oil was extracted using hydrodistillation method and extracts were prepared using different solvents viz. dichloromethane, hexane, and methanol. The pure compounds daucene, carotol, and daucol were isolated using column chromatography and derivatized using different reagents. The study demonstrated that antifungal potential of all tested compounds varied in a dose dependent manner. Structure activity relationship of isolated and derivatized compounds showed that polar moieties possessed more antifungal potential as compared to non-polar moieties. The results suggested that carrot seed methanol extract and carotol possessed strong antifungal potential as compared to other components tested. PRACTICAL APPLICATIONS: Phytopathogenic fungi are the major problems causing harmful damage to the rice crop. Only available control of these diseases is synthetic fungicides but their repeated use led to serious environmental issues, residual toxicity, and development of resistance. Therefore, it's better to find some natural alternatives. The current study was conducted to evaluate in vitro antifungal potential of carrot seed essential oil, its constituents and extracts against phytopathogenic fungi of rice. The methanol extract and carotol possessed highest antifungal potential which might be due to their polar nature. This information may add a new dimensions to biological activity of these natural molecules mainly in the field of agriculture as fungal diseases are found to be associated with major losses in agriculture. Hence these compounds can act as natural antifungal agents against rice fungi.

10.
Indian J Med Res ; 149(4): 517-527, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411176

RESUMO

Background & objectives: To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR. Methods: A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination. Results: Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region. Interpretation & conclusions: While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding for TB control in the Region.


Assuntos
Tuberculose Latente/epidemiologia , Modelos Teóricos , Tuberculose/epidemiologia , Humanos , Índia/epidemiologia , Tuberculose Latente/microbiologia , Tuberculose Latente/prevenção & controle , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Organização Mundial da Saúde
11.
J Clin Med ; 8(9)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461884

RESUMO

Raman spectroscopy (RS) is widely used as a non-invasive technique in screening for the diagnosis of oral cancer. The potential of this optical technique for several biomedical applications has been proved. This work studies the efficacy of RS in detecting oral cancer using sub-site-wise differentiation. A total of 80 samples (44 tumor and 36 normal) were cryopreserved from three different sub-sites: The tongue, the buccal mucosa, and the gingiva of the oral mucosa during surgery. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were used with principal component analysis (PCA) to classify the samples and the classifications were validated by leave-one-out-cross-validation (LOOCV) and k-fold cross-validation methods. The normal and tumor tissues were differentiated under the PCA-LDA model with an accuracy of 81.25% (sensitivity: 77.27%, specificity: 86.11%). The PCA-QDA classifier model differentiated these tissues with an accuracy of 87.5% (sensitivity: 90.90%, specificity: 83.33%). The PCA-QDA classifier model outperformed the PCA-LDA-based classifier. The model studies revealed that protein, amino acid, and beta-carotene variations are the main biomolecular difference markers for detecting oral cancer.

12.
Turk J Haematol ; 36(3): 193-198, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31042860

RESUMO

Objective: To evaluate the effectiveness of sequential compression devices (SCDs) for venous thromboembolism (VTE) prevention in medically ill hospitalized patients. Materials and Methods: Adult patients admitted to a teaching hospital from April 2015 to March 2016 were included. Patients on anticoagulants with or without SCDs were excluded. We analyzed VTE risk, length of hospital stay, and other comorbidities among propensity score-matched patients on SCDs and those without thromboprophylaxis (NONE). Results: Among 30,824 patients, 67 patients (0.22%) developed VTE during their hospital stays, with deep vein thrombosis (DVT) in 55 cases and pulmonary embolism (PE) in 12. VTE was seen in 47 out of 20,018 patients on SCDs (41 DVT, 6 PE) and 20 out of 10,819 patients without SCDs (14 DVT, 6 PE). Risk-adjusted analysis showed no significant difference in VTE incidence in the SCD group compared to NONE (odds ratio 0.99, 95% confidence interval 0.57-1.73, p=0.74). Conclusion: Compared to the NONE group, SCDs are not associated with decreased VTE incidence during hospital stay.


Assuntos
Anticoagulantes/uso terapêutico , Dispositivos de Compressão Pneumática Intermitente/tendências , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/farmacologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Stroke ; 50(5): 1089-1094, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31009343

RESUMO

Background and Purpose- Sickle cell disease (SCD) and arteriopathy are pediatric stroke risk factors that are not mutually exclusive. The relative contributions of sickled red blood cells and arteriopathy to stroke risk are unknown, resulting in unclear guidelines for primary and secondary stroke prevention when both risk factors are present. We hypothesized that despite similarities in clinical presentation and radiographic appearance of arteriopathies, stroke evaluation and management differ in children with SCD compared with those without SCD. Methods- We compared presentation and management of children with and without SCD enrolled in the IPSS (International Pediatric Stroke Study) with acute arterial ischemic stroke, according to SCD and arteriopathy status. Regression modeling determined relative contribution of SCD and arteriopathy in variables with significant frequency differences. Results- Among 930 childhood arterial ischemic strokes, there were 98 children with SCD, 67 of whom had arteriopathy, and 466 without SCD, 392 of whom had arteriopathy. Arteriopathy, regardless of SCD status, increased likelihood of hemiparesis (odds ratio [OR], 1.94; 95% CI, 1.46-2.56) and speech abnormalities (OR, 1.67; 95% CI, 1.29-2.19). Arteriopathy also increased likelihood of headache but only among those without SCD (OR, 1.89; 95% CI, 1.40-2.55). Echocardiograms were less frequently obtained in children with SCD (OR, 0.58; 95% CI, 0.37-0.93), but the frequency of identified cardiac abnormalities was similar in both groups ( P=0.57). Children with SCD were less likely to receive antithrombotic therapy, even in the presence of arteriopathy (OR, 0.14; 95% CI, 0.08-0.22). Arteriopathy was associated with a significantly higher likelihood of antithrombotic therapy in children without SCD (OR, 5.36; 95% CI, 3.55-8.09). Conclusions- Arteriopathy, and not SCD status, was most influential of stroke presentation. However, SCD status influenced stroke management because children with SCD were less likely to have echocardiograms or receive antithrombotic therapy. Further work is needed to determine whether management differences are warranted.


Assuntos
Anemia Falciforme/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Gerenciamento Clínico , Acidente Vascular Cerebral/diagnóstico por imagem , Adolescente , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia
14.
Int J Rheum Dis ; 22(2): 325-330, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26403216

RESUMO

Several ophthalmic manifestations in patients with dermatomyositis have been described but involvement of the retina is rare. A 39-year-old man diagnosed with dermatomysitis had developed sudden painless visual loss in the left eye. He was non-diabetic and non-hypertensive. He was on treatment with systemic prednisolone (50 mg/day) and methotrexate (7.5 mg/day) for dermatomyositis. His visual acuity was finger counting at 2 feet in the left eye and 6/6 in the right eye. Left fundus showed slight blurring of the optic disc margins, large peripapillary flame-shaped haemorrhages and extensive area of opacification suggestive of central retinal artery occlusion (CRAO) with sparing of the area supplied by the cilioretinal artery. The exact pathomechanism of CRAO in dermatomyositis remains poorly elucidated. The infarctive events following endothelial damage and platelet thrombi occurring in arterioles and capillaries of retina, optic disc and choriocapillaries causing ischemia/infarction have been suggested as possible reasons. However, central artery occlusion from high intraocular pressure from marked (heliotrope) orbital edema appears more plausible in our case. The degree of retinal damage is variable when CRAO lasts between 105 and 240 min and irreversible profound visual loss may occur from its occlusion lasting for more than 240 min. A prompt ophthalmological opinion/management is recommended to limit its progression.


Assuntos
Dermatomiosite/complicações , Oclusão da Artéria Retiniana/etiologia , Transtornos da Visão/etiologia , Adulto , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico , Recuperação de Função Fisiológica , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/tratamento farmacológico , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/tratamento farmacológico , Transtornos da Visão/fisiopatologia , Visão Ocular , Acuidade Visual
16.
Indian J Med Res ; 147(5): 496-500, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-30082574

RESUMO

Background & objectives: Ocular manifestations in HIV/AIDS patients range from adnexal disorders to the posterior segment disease. This study was aimed to evaluate the ocular manifestations, including vision-threatening manifestations in HIV-positive patients attending an antiretroviral therapy centre (ART) of a tertiary care hospital in north India and its association with the CD4+ cell count. Methods: This cross-sectional study was conducted in the department of Ophthalmology in collaboration with the ART centre. An equal number of patients were selected from each year. i.e: ., 30 patients each from those registered in the year 2010 till 2015. These patients were selected randomly from the register using systematic randomization. Hence, a total of 150 patients were examined for ocular manifestations. All the patients included in this study were on highly active ART. Results: Of the 150 patients examined, 53 per cent were females and 47 per cent were males. Heterosexual transmission was the most common mode of transmission in 126 (84%) patients. Maximum number of patients was in the age group of 31-40 yr. Ocular manifestations were present in 53 [35.3%; 95% confidence interval (CI): 28-43%] patients. Twelve (8%; 95% CI: 4-12%) patients had lid and adnexal manifestations. Anterior-segment manifestations were present in 20 (13.3%; 95% CI: 8-19%) patients. Posterior-segment manifestations were present in 21 (14%; 95% CI: 8-20%) and vision-threatening posterior-segment ocular lesions were present in 14 per cent of the patients. Univariate logistic regression showed a significant (P<0.001) inverse association of CD4+T-cell count with the vision-threatening posterior-segment ocular lesions. Interpretation & conclusions: Routine ocular examination may be done in all the HIV/AIDS patients to detect and treat vision-threatening ocular lesions at the earliest.


Assuntos
Oftalmopatias/virologia , Infecções por HIV/complicações , Adulto , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Índia , Masculino , Centros de Atenção Terciária
17.
BMJ Case Rep ; 20182018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29898908

RESUMO

Tumour lysis syndrome (TLS) is an oncological emergency. It is caused by cellular death occurring secondary to cancer therapy or spontaneously in rapidly dividing tumours. More common in haematological malignancies, it has also been reported in solid tumours. Out of 14 cases of small cell lung cancer (SCLC) with TLS, only three cases of spontaneous TLS have been reported in literature to date. Here we report a case of SCLC presenting as a spontaneous TLS.


Assuntos
Encefalopatias/complicações , Carcinoma Neuroendócrino/patologia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/complicações , Carcinoma de Pequenas Células do Pulmão/complicações , Síndrome de Lise Tumoral/etiologia , Idoso , Carcinoma Neuroendócrino/secundário , Serviço Hospitalar de Emergência , Evolução Fatal , Humanos , Neoplasias Hepáticas/secundário , Masculino , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Tomografia Computadorizada por Raios X/métodos
19.
Blood ; 131(20): 2183-2192, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29549173

RESUMO

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin (P = .007), lower indirect bilirubin (P = .005), and missense PKLR mutations (P = .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480.


Assuntos
Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Estudos de Associação Genética , Piruvato Quinase/deficiência , Erros Inatos do Metabolismo dos Piruvatos/diagnóstico , Adolescente , Adulto , Anemia Hemolítica Congênita não Esferocítica/etiologia , Anemia Hemolítica Congênita não Esferocítica/metabolismo , Anemia Hemolítica Congênita não Esferocítica/terapia , Transfusão de Sangue , Criança , Pré-Escolar , Colecistectomia/efeitos adversos , Colecistectomia/métodos , Terapia Combinada , Ativação Enzimática , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Piruvato Quinase/metabolismo , Erros Inatos do Metabolismo dos Piruvatos/etiologia , Erros Inatos do Metabolismo dos Piruvatos/metabolismo , Erros Inatos do Metabolismo dos Piruvatos/terapia , Esplenectomia/efeitos adversos , Esplenectomia/métodos , Avaliação de Sintomas , Resultado do Tratamento , Adulto Jovem
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