Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
J Hematol Oncol ; 12(1): 130, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801585

RESUMO

BACKGROUND: Treatment outcomes for patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain dismal. There are unmet needs for understanding the biologic basis of this malignancy using novel next-generation sequencing technologies. Herein, we investigated the clinical utility of circulating tumor DNA (ctDNA) (the liquid biopsy) in this malignancy. METHODS: ctDNA was analyzed in 112 patients with PDAC (54-73 genes) and tissue DNA in 66 patients (315 genes) (both clinical-grade next-generation sequencing). Number of alterations, %ctDNA, concordance between ctDNA and tissue DNA, and correlation of ctDNA results with survival were assessed. RESULTS: The most common genes altered in ctDNA were TP53 (46% of patients, N = 51) and KRAS (44%, N = 49). Median number of characterized ctDNA alterations per patient was 1 (range, 0-6), but patients with advanced PDAC had significantly higher numbers of ctDNA alterations than those with surgically resectable disease (median, 2 versus 0.5, P = 0.04). Overall, 75% (70/94) of advanced tumors had ≥ 1 ctDNA alteration. Concordance rate between ctDNA and tissue DNA alterations was 61% for TP53 and 52% for KRAS. Concordance for KRAS alterations between ctDNA and tissue DNA from metastatic sites was significantly higher than between ctDNA and primary tumor DNA (72% vs 39%, P = 0.01). Importantly, higher levels of total %ctDNA were an independent prognostic factor for worse survival (hazard ratio, 4.35; 95% confidence interval, 1.85-10.24 [multivariate, P = 0.001]). A patient with three ctDNA alterations affecting the MEK pathway (GNAS, KRAS, and NF1) attained a response to trametinib monotherapy ongoing at 6 months. CONCLUSIONS: Our findings showed that ctDNA often harbored unique alterations some of which may be targetable and that significantly greater numbers of ctDNA alterations occur in advanced versus resectable disease. Furthermore, higher ctDNA levels were a poor prognostic factor for survival.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31786737

RESUMO

PURPOSE: Reducing the dosing frequency of antipsychotics (APs) with long-acting injectables (LAIs) such as once-monthly paliperidone palmitate (PP1M) can improve adherence and clinical outcomes for schizophrenia patients. This US study compared physical and psychiatric comorbidity-related outcomes, AP adherence, healthcare resource utilization (HRU), and costs pre- and post-transition to PP1M among schizophrenia patients treated with oral risperidone/paliperidone pre-PP1M transition. METHODS: Health insurance claims from the IQVIA™ PharMetrics Plus database (01/01/2012-07/31/2018) were used to identify adults with ≥ 2 schizophrenia diagnoses, ≥ 1 claim for PP1M, and ≥ 30 days of treatment with oral risperidone/paliperidone in the 60 days before the first PP1M claim (i.e., the index date). Comorbidity-related outcomes, adherence to APs (measured via the proportion of days covered [PDC]), all-cause per-patient-per-month (PPPM) HRU, and all-cause PPPM medical, pharmacy, and total costs (i.e., sum of medical and pharmacy costs) during the 6-month periods pre- and post-transition to PP1M were compared using generalized estimating equation models adjusted for repeated measurements. Analyses were replicated in the subset of patients with ≥ 1 all-cause inpatient stay pre-PP1M transition. FINDINGS: Among 427 schizophrenia patients transitioning from oral risperidone/paliperidone to PP1M, the mean age was 41.1 years and 37.9% were female. Following the PP1M transition, patients were less likely to have claims with a diagnosis for psychoses (odds ratio [OR] 0.41; P < 0.001), hypertension (OR 0.80; P = 0.011), depression (OR 0.70; P < 0.001), drug abuse (OR 0.60; P < 0.001), substance-related and addictive disorders (OR 0.73; P = 0.003), bipolar and related disorders (OR 0.59; P < 0.001), sleep-wake disorders (OR 0.68; P = 0.017), anxiety disorders (OR 0.78; P = 0.034), and other conditions that may require a focus of clinical attention (OR 0.58; P < 0.001). Mean PDC by APs was higher post-PP1M (mean = 0.81) versus pre-PP1M (mean = 0.68) transition. Post-PP1M, patients were less likely to have an all-cause emergency room visit (OR 0.51; P < 0.001) or inpatient stay (OR 0.39; P < 0.001) compared to pre-PP1M. All-cause total healthcare costs remained similar post- versus pre-transition to PP1M (mean monthly cost difference [MMCD] = $228; P = 0.260). Pharmacy costs increased post-PP1M (MMCD = $960; P < 0.001), but were offset by decreasing medical costs (MMCD = - $732; P < 0.001), largely driven by lower costs related to inpatient stays (MMCD = - $695; P < 0.001) and emergency room visits (MMCD = - $63; P < 0.001). For patients with ≥ 1 all-cause inpatient stay pre-PP1M transition (N = 177), a more pronounced improvement in comorbidity-related outcomes, a more pronounced reduction in HRU, and a reduction in total healthcare costs (MMCD = - $1308; P < 0.001) were observed post-transition to PP1M. IMPLICATIONS: Among schizophrenia patients in the US, transitioning to PP1M following oral risperidone/paliperidone treatment was associated with improved comorbidity-related outcomes, higher adherence, and a reduction in HRU, while remaining cost neutral. Furthermore, patients with ≥ 1 all-cause inpatient stay pre-PP1M transition had significantly lower total healthcare costs post-PP1M transition.

4.
Adv Ther ; 36(10): 2941-2953, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396809

RESUMO

INTRODUCTION: There is limited literature on treatment patterns, healthcare resource utilization (HRU), and costs among patients who transition from once-monthly paliperidone palmitate (PP1M) to once-every-3-month paliperidone palmitate (PP3M) in a real-world setting. Hence, this study compared treatment patterns, HRU, and costs 12-month pre- and post-PP3M transition among Veteran's Health Administration (VHA) patients with schizophrenia. METHODS: Patients with schizophrenia (aged ≥ 18 years) who initiated PP1M and transitioned per on-label criteria to PP3M (no treatment gap of > 45 days in PP1M during the 4 months prior, same dose strength of the last two PP1M claims, and appropriate dose conversion from last PP1M to first PP3M claim) from January 2015 to March 2017 were included from the VHA database. The first transition date to PP3M was identified as the index date. Patients were required to have 12-month pre- and post-PP3M continuous health plan eligibility. Outcomes were compared using the Wilcoxon-signed rank and McNemar's test, appropriately. RESULTS: The study included 122 patients [mean (SD) age: 54 (13.7) years]. Pre- and post-PP3M transition, 64.8% and 61.5% of patients were adherent (proportion of days covered ≥ 80%) to PP1M and PP3M, respectively. Comparison of HRU outcomes pre- and post-PP3M transition exhibited lower all-cause outpatient (37.5 vs. 31.1, p < 0.0001) and pharmacy visits (56.1 vs. 46.7, p < 0.0001). Similar trends were seen for mental health and schizophrenia-related outpatient and pharmacy HRU. Comparison of cost outcomes resulted in lower all-cause outpatient ($27,221 vs. $22,356, p = 0.0033), higher pharmacy ($16,349 vs. $17,003, p = 0.0076), lower total medical ($35,834 vs. $28,900, p = 0.0257), and no difference in total costs ($52,183 vs. $45,903, p = 0.3118). Similar trends were seen for mental health and schizophrenia-related costs. CONCLUSIONS: Transition to PP3M was associated with a decline in outpatient and pharmacy visits. All-cause medical cost reduction fully offset increased pharmacy costs among VHA patients with schizophrenia who transitioned from PP1M to PP3M. FUNDING: Janssen Scientific Affairs.

5.
Indian J Microbiol ; 59(3): 266-272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31388203

RESUMO

Dandruff is one of the most common clinically manifested and studied scalp disorders. It has been associated with both bacteria and fungi. Bacteria and fungi inhabiting the scalp are known to influence each other and manifestation of dandruff. Fungal and bacterial isolates from scalp epithelial flakes (dandruff) were identified by rDNA sequencing. Local oils were tested for fungal and bacterial inhibition, interaction and biofilm formation, cell-cell interactions were studied by auto aggregation and surface thermodynamics studies. The isolates Bacillus sp.C2b1 (MK036745) and Malassezia sp. C2y1 (MK036746) were inhibited by Mahabhrungraj oil. The fungal morphological switch was evident and dependent on nutrition. Cell aggregation studies suggested the interaction of bacteria with yeast (non-pathogenic) phase of the fungus. Bacterial and yeast cells were found to be compatible for biofilm formation. The fungal mycelial surfaces were found to be conducive for interaction with both bacterial cells and yeast forms. The results here indicate the significance of mycelial phase of scalp-isolated fungus in interaction with the bacterial surfaces and also with self-yeast phase surface. This is the first report of the interaction between scalp-isolated microorganisms with respect to their surface interaction capabilities.

6.
Curr Med Res Opin ; 35(12): 2159-2168, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31366251

RESUMO

Objective: To address gaps in the literature on healthcare resource utilization (HRU) and costs among patients with schizophrenia and prior hospitalization who transition from oral risperidone or paliperidone (oral ris/pali) to once-monthly paliperidone palmitate (PP1M) in a real-world setting by comparing treatment patterns, HRU, and costs 12-months pre- and post-transition to PP1M among Veterans Health Administration (VHA) patients affected by schizophrenia who have had ≥1 hospitalization.Methods: VHA patients with schizophrenia (aged ≥18 years) who initiated oral ris/pali, had ≥1 all-cause inpatient stay, and transitioned to PP1M from January 2015-March 2017 were included from the VHA database. The first transition date to PP1M was identified as the index date. Patients were required to have continuous health plan eligibility for 12 months pre- and post-PP1M. Outcomes were compared using the Wilcoxon signed-rank and McNemar's test, as appropriate.Results: The study included 319 patients (mean [SD] age = 51.6 [4.2] years) during 12 months of baseline and follow-up. During pre-PP1M transition, 7.2% of the patients were adherent (proportion of days covered [PDC] ≥ 80%) to oral ris/pali. Post-PP1M transition, 27.6% of the patients were adherent to PP1M. Comparison of HRU outcomes from the pre- to post-PP1M transition revealed significantly lower all-cause inpatient stays (3.5 vs 1.4, p < .0001) and shorter inpatient length of stay (43.4 vs 18.3 days, p < .0001). Similar trends were seen for mental health and schizophrenia-related HRU. Cost outcome comparison indicated significantly lower all-cause inpatient costs ($64,702 vs $24,147, p < .0001), total medical costs ($87,917 vs $56,947, p < .0001), and total costs ($91,181 vs $69,106, p < .0001). A similar trend was observed for mental health and schizophrenia-related costs.Conclusions: Transitioning from oral ris/pali to PP1M may significantly improve HRU and provide potential cost savings in VHA patients with schizophrenia and ≥1 prior hospitalization.

7.
Adv Ther ; 36(4): 858-869, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30848442

RESUMO

INTRODUCTION: Factors underlying the selection of antipsychotics for patients with schizophrenia are poorly understood. This study investigated variables associated with initiation of treatment with the long-acting injectables paliperidone palmitate (LAI-PP) and aripiprazole LAI (LAI-AP) in Medicaid patients with schizophrenia. METHODS: Adults with at least one medical or pharmacy claim for LAI-PP or LAI-AP from 1 January 2013 to 31 December 2016 were selected from the IBM® MarketScan® Medicaid Database. The date of the first LAI-PP or LAI-AP claim was the index date. Patients who had at least two medical claims, on different days, for a schizophrenia diagnosis and at least 12 months of continuous health plan enrollment prior to index date were included in the analysis. Multivariable logistic regression was performed to determine the factors associated with the initiation of LAI-PP versus LAI-AP. RESULTS: Of included patients, 5501 initiated LAI-PP and 1449 initiated LAI-AP. Patients more likely to initiate LAI-PP versus LAI-AP were older, male, or African American (all p < 0.01). Patients with obesity (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.71, 0.98), post-traumatic stress disorder (OR 0.76; 95% CI 0.63, 0.92), or prior oral antipsychotic use (OR 0.66; 95% CI 0.55, 0.79) were less likely to initiate LAI-PP; whereas, patients with nonorganic psychoses (OR 1.35; 95% CI 1.18, 1.55) or prior use of other injectable antipsychotics (OR 1.26; 95% CI 1.09, 1.47) were more likely to initiate LAI-PP versus LAI-AP. Patients with at least two all-cause hospitalizations were 1.37 times more likely to initiate LAI-PP vs LAI-AP (OR 1.37; 95% CI 1.18, 1.60). CONCLUSION: Factors associated with initiating LAI-PP and LAI-AP differed. Notably, patients who initiated LAI-PP had greater prior use of medical services than LAI-AP patients. Understanding prescribing practices may help optimize treatment strategies and improve disease management. FUNDING: Janssen Scientific Affairs, LLC.

8.
Food Chem ; 288: 208-214, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30902283

RESUMO

Cucumber (Cucumis sativus L.) is a rich source of vitamins, minerals, and antioxidants. Its post-harvest deterioration leads to a limited shelf-life up to 5-7 days. To avoid such loss, the present study investigates the potential effect of starch glucose (SG) coating on the extension of its shelf-life, after harvest. 1.0, 1.5 and 2.0 µM of starch with 2.5 µM D-glucose solutions were coated over freshly harvested cucumbers and stored at refrigerated temperature (±4 °C) for 30 days. 1.5 µM starch plus 2.5 µM D-glucose displayed significantly better results as per the skin colour and sensory evaluation test. This level of SG coating extended the shelf-life of cucumbers up to 30 days with least reduction in weight loss, total soluble sugar, protein, catalase activity, peroxidase activity and increased in proline content, 2, 2-diphenyl-1-picrylhydrazyl antioxidant activities and ferrous ion chelating activities.


Assuntos
Cucumis sativus/química , Glucose/química , Amido/química , Antioxidantes/química , Conservação de Alimentos
9.
Curr Med Res Opin ; 35(3): 407-416, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30556739

RESUMO

OBJECTIVES: To compare comorbidity-related outcomes, adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs pre- and post-transition to once-every-3-months paliperidone palmitate (PP3M) in commercially-insured patients with schizophrenia. METHODS: Adults with ≥1 claim for PP3M, ≥2 schizophrenia diagnoses, and adequate treatment with once-monthly paliperidone palmitate (PP1M; i.e. no gap of >45 days in PP1M coverage for ≥4 months, same PP1M dosage for the last two PP1M claims, and appropriate PP1M to PP3M dosing conversion) were selected from the IQVIA PharMetrics Plus database (May 2014-February 2018). Generalized estimating equation models adjusted for repeated measurements were used to compare patient characteristics, adherence to APs, HRU, and costs during the 6-month period pre- vs post-transition to PP3M. RESULTS: Of 152 included patients, the mean age was 41.0 years and 36.2% were females. Post-PP3M transition, patients were less likely to have a claim with a diagnosis for substance-related and addictive disorders (odds ratio [OR] = 0.57), psychoses (OR = 0.57), diabetes without chronic complication (OR = 0.72), and drug abuse (OR = 0.64; all p < .05). Patients were more likely to be adherent to APs (OR = 2.01, p = .007), compared to the period pre-PP3M transition. There was no significant difference in HRU pre- vs post-transition. All-cause total (mean monthly cost difference [MMCD] = $242), pre-rebate pharmacy (MMCD = $65), and medical costs (MMCD = $176) remained similar pre- vs post-transition (all p > .05). CONCLUSIONS: Transitioning to PP3M was associated with an improvement in adherence and in comorbidity-related outcomes related to substance-related and addictive disorders, psychoses, diabetes without chronic complication, and drug abuse. These findings suggest PP3M may enhance comorbidity-related outcomes and adherence while remaining cost neutral.


Assuntos
Antipsicóticos/administração & dosagem , Palmitato de Paliperidona/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Conf Proc IEEE Eng Med Biol Soc ; 2018: 2016-2019, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30440796

RESUMO

Electroencephalography (EEG) based brain computer interfaces (BCI) introduces promising communication pathway between the brain and external devices, not only for the motor-impaired but also the healthy users. However, the current EEG-based interface device is not convenient enough for daily uses. In this study, we developed an EEG acquisition system that records brain signals without contacting scalp. The proposed system consists of a small sized ($5.5\,\times 3\,\mathrm{cm}^{2}$ acquisition hardware and four stainless steel electrodes integrated in a regular sport hat. To demonstrate the concept, we used an in-house developed steady-state visual evoked potentials (SSVEP) paradigm and recorded EEG signals using the proposed system. The EEG signals were compared with three different brain states - Eye Closed, Eye Open, and Visual Stimulation. The results show that the BCI system can record SSVEP from the brain without any professional setups or expensive dry-electrodes.


Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia/instrumentação , Potenciais Evocados Visuais , Dispositivos Eletrônicos Vestíveis , Algoritmos , Encéfalo , Humanos , Estimulação Luminosa
11.
Curr Med Res Opin ; 34(8): 1475-1481, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29661086

RESUMO

OBJECTIVE: This study aimed to describe real-world experiences following a non-medical switch among adults with type 2 diabetes mellitus (T2DM) in the United States. METHODS: For this cross-sectional study, patients with T2DM (N = 451) provided data on demographics, and how a non-medical switch of their anti-hyperglycemic agent (AHA) affected their general health, HbA1c levels and medication management, via an Internet-based survey. Patients self-reported their level of satisfaction with the original medication and emotional reactions to the non-medical switch. Patients who recently experienced a non-medical switch of their AHA(s) (n = 379) were asked about the consequences of switching and their satisfaction with the switch (vs. the original) medication. RESULTS: Patients most frequently reported feeling very/extremely frustrated, surprised, upset and angry in reaction to a non-medical switch. Patients were somewhat satisfied with their original medication. Between 20% and 30% of patients reported the non-medical switch had a moderate/major effect on their general health, diabetes, mental well-being and control over their health. The blood glucose levels of recent switchers were somewhat/much worse (20.7%) and medication management was somewhat/much worse (12.9%) on the switch (vs. the original) medication. Some recent switchers reported old symptoms returning (7.7%) and experiencing new side-effects (14.2%). CONCLUSIONS: Approximately one in five patients reported a moderate/major negative impact on their blood glucose level, diabetes, mental well-being, general health and control over their health following a non-medical switch. Findings suggest that a non-medical switch may have unintended negative health consequences and results in considerable burden across multiple domains for a sizeable minority of patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Glicemia/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
12.
Curr Med Res Opin ; 34(6): 1143-1152, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29595326

RESUMO

OBJECTIVE: This US retrospective cohort study compared the real-world effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg on HbA1c reduction in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients initiated on canagliflozin 300 mg or dapagliflozin 10 mg were identified from de-identified claims data in the Optum Clinformatics database (1 January 2014-30 September 2016). Propensity score matching was used to create balanced cohorts. The primary outcome was the proportion of patients with HbA1c <8.0% (HEDIS target); secondary outcomes included the proportion of patients with HbA1c <7.0% (ADA target) and >9.0% (HEDIS poor control), absolute change in HbA1c, and treatment patterns. RESULTS: At 6 months post-index (intent-to-treat population), a significantly higher proportion of patients in the canagliflozin 300 mg versus dapagliflozin 10 mg cohort achieved HbA1c <8.0% (70.8% vs. 59.1%; OR [95% CI]: 1.60 [1.26, 2.04]; p = .0001) and HbA1c <7.0% (36.7% vs. 25.1%; OR [95% CI]: 1.75 [1.34, 2.27]; p < .0001). A similar proportion of patients had HbA1c >9.0%. Mean HbA1c reduction was -1.17% with canagliflozin 300 mg and -0.91% with dapagliflozin 10 mg (difference of -0.26%; p = .0049). HbA1c results from a sensitivity analysis in the on-treatment population were consistent with the primary analysis. Patients in the canagliflozin 300 mg versus dapagliflozin 10 mg cohort were less likely to discontinue treatment (OR [95% CI]: 0.75 [0.57, 0.99]; p = .0400) or switch medication (OR [95% CI]: 0.72 [0.54, 0.96]; p = .0229). CONCLUSIONS: In this real-world study, patients with T2DM initiated on canagliflozin 300 mg had better HbA1c goal attainment and larger HbA1c reduction than patients initiated on dapagliflozin 10 mg.


Assuntos
Compostos Benzidrílicos , Canagliflozina , Diabetes Mellitus Tipo 2 , Glucosídeos , Hemoglobina A Glicada/análise , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Canagliflozina/administração & dosagem , Canagliflozina/efeitos adversos , Estudos de Coortes , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Pontuação de Propensão , Projetos de Pesquisa , Estudos Retrospectivos , Estados Unidos/epidemiologia
13.
Int J Surg Pathol ; 26(4): 347-352, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29207904

RESUMO

Gastrointestinal (GI) graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infection often simulate each other. However, distinction between GVHD and CMV infection is critical in the management of immunosuppression for transplant recipients. This study retrospectively reviewed 16 patients diagnosed with GVHD from 2010 to 2016 and found 4 cases (25%) coinfected with CMV. Two cases were initially diagnosed as GVHD only but found to have CMV infection by serological testing within 3 days after immunosuppression treatment for GVHD. The remarkable histological feature of CMV infection appeared to be significant acute inflammation in addition to apoptotic epithelial injuries, and particularly in an early stage of CMV replication, acute inflammation is possibly the only detectable feature of CMV infection.


Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/virologia , Adulto , Idoso , Criança , Infecções por Citomegalovirus/imunologia , Feminino , Gastroenteropatias/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Adulto Jovem
14.
Biomed Opt Express ; 7(11): 4763-4768, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27896014

RESUMO

A critical consideration for whole slide imaging (WSI) platform is to perform accurate autofocusing at high speed. Typical WSI systems acquire a z-stack of sample images and determine the best focal position by maximizing a figure of merit. This strategy, however, has suffered from several limitations, including low speed due to multiple image acquisitions, relatively low accuracy of focal plane estimation, short axial range for autofocusing, and difficulties in handling transparent samples. By exploring the autocorrelation property of the tissue sections, we report a novel single-frame autofocusing scheme to address the above challenges. In this approach, we place a two-pinhole-modulated camera at the epi-illumination arm. The captured image contains two copies of the sample separated by a certain distance. By identifying this distance, we can recover the defocus distance of the sample over a long z-range without z-scanning. To handle transparent samples, we set an offset distance to the autofocusing camera for generating out-of-focus contrast in the captured image. The single-frame nature of our scheme allows autofocusing even when the stage is in continuous motion. We demonstrate the use of the our autofocusing scheme for fluorescence WSI and quantify the focusing performance on 1550 different tissue tiles. The average autofocusing error is ~0.11 depth-of-field, 3 folds better than that of conventional methods. We report an autofocusing speed of 0.037 s per tile, which is much faster than that of conventional methods. The autofocusing range is ~80 µm, 8 folds longer than that of conventional methods. The reported scheme is able to solve the autofocusing challenges in WSI systems and may find applications in high-throughput brightfield/fluorescence WSI.

15.
Cancer Med ; 5(10): 2841-2847, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27666740

RESUMO

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis (CP), IPMN, or pancreatic carcinoma (PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 ± 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 ± 0.16 for correctly classified lesions and 0.47 ± 0.10 for incorrectly classified lesions (P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/classificação , Carcinoma Papilar/classificação , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/classificação
16.
J Control Release ; 239: 223-30, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27574992

RESUMO

Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for (99m)Tc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with (99m)Tc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with (99m)Tc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with (99m)Tc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of (18)F-fluorodeoxyglucose ((18)F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro(99m)Tc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04±0.52nM. In cancer xenografts, (99m)Tc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (P<0.01) with blockade. No radioactive uptake was observed in the PC3 tumors with (99m)Tc-TCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by (18)F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions.


Assuntos
Neoplasias do Colo/diagnóstico por imagem , Imagem Molecular/métodos , Fragmentos de Peptídeos/administração & dosagem , Tecnécio/administração & dosagem , Animais , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células HCT116 , Humanos , Camundongos , Camundongos SCID , Fragmentos de Peptídeos/metabolismo , Ligação Proteica/fisiologia , Tecnécio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
17.
BMC Health Serv Res ; 16(a): 356, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27495291

RESUMO

BACKGROUND: The randomized, double-blind CANTATA-SU (CANagliflozin Treatment And Trial Analysis Sulfonyl Urea) clinical trial compared the use of canagliflozin (100 mg or 300 mg) and maximally tolerated glimepiride (6-8 mg) over 104 weeks as add-on therapy for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Compared with glimepiride, canagliflozin use was associated with durable reductions in glycated hemoglobin (A1C), blood pressure (BP), and body weight. The aim of this post-hoc analysis of the CANTATA-SU trial was to assess the comparative efficacy of canagliflozin and glimepiride in the attainment of recently updated diabetes-related quality measures (QMs) for up to 104 weeks of treatment. METHODS: This post-hoc analysis evaluated the proportions of patients achieving individual diabetes-related QMs using data from the randomized, double-blind, Phase 3 CANTATA-SU trial. Change in A1C from baseline, and proportions of the study population achieving QMs: A1C <7.0 %, <8.0 %, and >9.0 % were assessed. Secondary endpoints included change in BP from baseline, and the proportions of the study population achieving QMs related to BP and body weight. RESULTS: The proportions of patients in the canagliflozin 100 mg, canagliflozin 300 mg, and glimepiride groups meeting criteria for all QMs were similar at baseline. At 52 and 104 weeks of treatment, canagliflozin 100 mg and canagliflozin 300 mg provided better or similar reductions in A1C from baseline and achievement of glycemic control QMs compared with glimepiride. At 52 and 104 weeks of treatment, the attainment of QMs related to reductions in body weight and BP all favored canagliflozin compared with glimepiride. Canagliflozin was associated with lower incidence of documented hypoglycemia and severe hypoglycemia compared with glimepiride. CONCLUSIONS: Using the recently adjusted and currently accepted diabetes-related QMs, this analysis observed superior glycemic control with canagliflozin compared with maximally tolerated glimepiride in patients with T2DM who were previously poorly controlled on metformin monotherapy. Compared with maximally tolerated glimepiride, canagliflozin resulted in better achievement of diabetes-related QMs related to weight loss and BP, and was associated with lower incidences of hypoglycemic events. TRIAL REGISTRATION: Clinical trial registry name: CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride. CLINICAL TRIAL REGISTRATION NUMBER: NCT00968812 , registered August 28, 2009.


Assuntos
Canagliflozina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Indicadores de Qualidade em Assistência à Saúde , Compostos de Sulfonilureia/administração & dosagem , Idoso , Glicemia , Determinação da Pressão Arterial , Método Duplo-Cego , Feminino , Glucosídeos/uso terapêutico , Hemoglobina A Glicada , Humanos , Hipoglicemia , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiofenos/uso terapêutico , Resultado do Tratamento
18.
Case Rep Pathol ; 2016: 4704781, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27429820

RESUMO

Intrabiliary metastasis from colorectal carcinoma (CRC) growing within or invading bile ducts is not a very common pattern. However, accurate diagnosis of metastatic lesions is very important for selection of adjuvant therapy and prognosis. We report a case of 71-year-old male who developed painless jaundice due to hepatobiliary obstruction. MRI demonstrated 1.4 cm intraductal mass at hepatic hilum with severe intrahepatic ductal dilation, consistent with cholangiocarcinoma. ERCP (endoscopic retrograde cholangiopancreatography) showed intraductal segmental biliary stricture. Biopsy from the lesion showed adenocarcinoma favoring primary cholangiocarcinoma due to the papillary morphology and location of the mass. His past history was significant for rectosigmoid carcinoma (pT1N0) ten years ago and liver resection for metastatic CRC four years ago. He subsequently underwent central hepatectomy with resection of common bile duct. Grossly, there was a 1.2 cm intraductal mass at the bifurcation of bile ducts with multiple nodules in liver parenchyma. Microscopic examination revealed intraductal carcinoma with papillary architecture colonizing bile duct epithelium with resultant dilation and tortuosity. Occasional liver parenchymal nodules show classical metastatic pattern resembling CRC. Because of two distinct morphologic patterns and patient's past history, immunostains were performed. CK7 stained uninvolved bile duct epithelium with no staining in intrabiliary metastatic growth. CK20 and CDX2 were positive, thus confirming intrabiliary growth as metastatic growth from CRC. In summary, findings from our case indicate that intrabiliary growth of metastatic CRC can easily be overlooked with major duct involvement. Pathologic evaluation with use of immunohistochemical stains is very important to achieve correct diagnosis.

19.
Case Rep Pathol ; 2016: 1738696, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27110418

RESUMO

We report a rare association of hepatocellular carcinoma with familial adenomatous polyposis in a young patient and its clinical significance. A 28-year-old female with a past medical history of familial adenomatous polyposis (FAP) and subsequent colonic adenocarcinoma underwent total colectomy. She later presented with intermittent right upper quadrant pain and nausea of four months' duration. MRI of the abdomen revealed multiple liver lesions, the largest 8.5 cm in diameter, with radiologic features suggestive of hepatocellular carcinoma. A CT-guided liver biopsy demonstrated well-differentiated HCC which was confirmed by immunohistochemistry. In patients with a history of FAP, a heightened awareness of the possibility of concurrent or subsequent HCC is warranted.

20.
Biomed Opt Express ; 7(1): 148-57, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26819824

RESUMO

Barrett's esophagus (BE) is a metaplastic disorder where dysplastic and early cancerous changes are invisible to the naked eye and where the practice of blind biopsy is hampered by large sampling errors. Multi-photon microscopy (MPM) has emerged as an alternative solution for fast and label-free diagnostic capability for identifying the histological features with sub-micron accuracy. We developed a compact, inexpensive MPM system by using a handheld mode-locked fiber laser operating at 1560nm to study mucosal biopsies of BE. The combination of back-scattered THG, back-reflected forward THG and SHG signals generate images of cell nuclei and collagen, leading to label-free diagnosis in Barrett's.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA