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OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Infants with BPD are at increased risk for pulmonary hypertension (PH). Cardiac catheterization is the gold standard for diagnosing PH, but cardiac catheterization is challenging to perform in small, sick, premature infants. The utility of echocardiography for diagnosing PH and predicting outcomes in extremely premature infants has not been clearly defined. Therefore, we sought to use predefined criteria to diagnose PH by echocardiogram and relate PH severity to mortality in extremely premature infants with BPD. STUDY DESIGN: Echocardiograms from 46 infants born ≤28 weeks' postmenstrual age with a diagnosis of BPD were assessed for PH by three pediatric cardiologists using predefined criteria, and survival times among categories of PH patients were compared. A total of 458 echocardiograms were reviewed, and 15 (33%) patients were found to have at least moderate PH. Patients with at least moderate PH had similar demographic characteristics to those with no/mild PH. RESULTS: Ninety percent of infants without moderate to severe PH survived to hospital discharge, compared with 67% of infants with at least moderate PH (p = 0.048). Patients with severe PH had decreased survival to hospital discharge (38%) compared with moderate (100%) and no/mild PH (90%) groups. Kaplan-Meier survival curves also differed among PH severity groups (Wilcoxon p < 0.001). CONCLUSION: Using predefined criteria for PH, premature infants with BPD can be stratified into PH severity categories. Patients diagnosed with severe PH by echocardiogram have significantly reduced survival. KEY POINTS: · A composite score definition of PH by echocardiogram showed high inter- and intrarater reliability.. · Infants with severe PH by echocardiogram had decreased survival rates.. · Early diagnosis of PH by echocardiogram dictates treatment which may improve outcomes..
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Background: Treatment with methadone is effective in reducing heroin use, HIV risk, and death; however, not all patients respond to treatment. Better outcomes may emerge with personalized treatment based on factors that influence treatment courses. Objectives: To investigate psychosocial variables contributing to treatment response, using a comprehensive definition of treatment response. Methods: Seventy participants seeking treatment for heroin and cocaine addiction completed up to 40 weeks of daily methadone. At week 22, we administered a semi-structured interview for DSM-IV symptoms. We defined opioid treatment responders as people still enrolled at 22 weeks, not meeting past 30-day criteria for DSM-IV opioid abuse or dependence or DSM-5 opioid use disorder, and providing ≥75% opioid-negative urine samples in the 30 days prior to week 22. The same criteria were applied to assess cocaine treatment response. Results: Sample was 71% male, 41% White, and averaged 39.4 ± 7.9 years old. Opioid treatment response was more likely in participants who had been employed over the past 3 years (OR: 8.1, 95% CI: 1.2-55) and less likely in those who spent more time on hobbies (OR: 0.45, 95% CI: 0.23-0.88). Cocaine treatment response was more likely in participants who had a good relationship with their father (OR: 5.3, 95% CI: 1.2-24) and less likely if positive for hepatitis C (OR: 0.15, 95% CI: 0.03-0.75). Conclusions: Pretreatment characteristics differentially predict treatment response for heroin and cocaine use. Similar research in diverse patient groups may aid in the development of personalized treatment combining biologic treatment with targeted psychosocial interventions.
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Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dependência de Heroína/tratamento farmacológico , Metadona/uso terapêutico , Entorpecentes/uso terapêutico , Adulto , Emprego , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos , Prognóstico , Resultado do TratamentoRESUMO
Cells respond to genotoxic insults such as ionizing radiation by halting in the G2 phase of the cell cycle. Delayed cell death (mitotic death) can occur when the cell is released from G2, and specific spindle defects form endopolyploid cells (endoreduplication/tetraploidy). Enhanced G2 chromosomal radiosensitivity has been observed in many cancers and genomic instability syndromes, and it is manifested by radiation-induced chromatid aberrations observed in lymphocytes of patients. Here we compare the G2 chromosomal radiosensitivity in prostate patients with benign prostatic hyperplasia (BPH) or prostate cancer with disease-free controls. We also investigated whether there is a correlation between G2 chromosomal radiosensitivity and aneuploidy (tetraploidy and endoreduplication), which are indicative of mitotic cell death. The G2 assay was carried out on all human blood samples. Metaphase analysis was conducted on the harvested chromosomes by counting the number of aberrations and the mitotic errors (endoreduplication/tetraploidy) separately per 100 metaphases. A total of 1/14 of the controls were radiosensitive in G2 compared to 6/15 of the BPH patients and 15/17 of the prostate cancer patients. Radiation-induced mitotic inhibition was assessed to determine the efficacy of G2 checkpoint control in the prostate patients. There was no significant correlation of G2 radiosensitivity scores and mitotic inhibition in BPH patients (P = 0.057), in contrast to prostate cancer patients, who showed a small but significant positive correlation (P = 0.029). Furthermore, there was no significant correlation between G2 radiosensitivity scores of BPH patients and endoreduplication/ tetraploidy (P = 0.136), which contrasted with an extremely significant correlation observed in prostate cancer patients (P < 0.0001). In conclusion, cells from prostate cancer patients show increased sensitivity to the induction of G2 aberrations from ionizing radiation exposure but paradoxically show reduced mitotic indices and aneuploidy as a function of aberration frequency.
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Cromossomos Humanos/efeitos da radiação , Fase G2/genética , Hiperplasia Prostática/radioterapia , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Reparo do DNA , Humanos , Masculino , Pessoa de Meia-Idade , Mitose/efeitos da radiação , Poliploidia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Tolerância a RadiaçãoRESUMO
BACKGROUND: Tumor ablation as a means of treating breast cancer is being investigated. Microwave energy is promising because it can preferentially heat high-water-content breast carcinomas, compared to adipose and glandular tissues. METHODS: This is a prospective, multicenter, nonrandomized dose-escalation study of microwave treatment. Thermal dose was measured as (1) thermal equivalent minutes (cumulative equivalent minutes; CEM) of treatment relative to a temperature of 43 degrees C and (2) peak tumor temperature. Microwaves were guided by an antenna-temperature sensor placed percutaneously into the tumor. Outcomes measured were pathologic response (tumor necrosis) side effects. RESULTS: Twenty-five patients (mean age, 57 years) were enrolled. The mean tumor diameter was 1.8 cm. Tumoricidal temperatures (>43 degrees C) were reached in 23 patients (92%). Tumor size was unchanged after thermotherapy (P = not significant). Pathologic necrosis was achieved in 17 (68%) patients. Complete necrosis of the invasive component was achieved in two patients. One hundred forty CEM is predictive of a 50% tumor response, and 210 CEM is predictive of a 100% tumor response (P =.003). Univariate linear regression predicts that peak tumor temperatures of 47.4 degrees C and 49.7 degrees C cause a 50% tumor response and a 100% tumor response, respectively. CONCLUSIONS: Thermotherapy causes tumor necrosis and can be performed safely with minimal morbidity. The degree of tumor necrosis is a function of the thermal dose. Future studies will evaluate the impact of high doses of thermotherapy on margin status and complete tumor ablation.
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Neoplasias da Mama/terapia , Hipertermia Induzida/métodos , Micro-Ondas/uso terapêutico , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Modelos Lineares , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Estudos ProspectivosRESUMO
BACKGROUND: A pilot safety study of focused microwave phased array thermotherapy in the treatment of primary breast carcinomas was conducted. METHODS: Ten patients with breast carcinomas beneath the skin surface that ranged in maximal clinical size from 1 to 8 cm (mean, 4.3 cm) were treated with the breast compressed in the prone position. We planned to deliver a tumor thermal dose equivalent to 60 minutes at 43 degrees C. Breast imaging and pathology data were used to assess efficacy. RESULTS: For the 10 patients, the mean tumor equivalent thermal dose was 51.7 minutes, the mean peak tumor temperature was 44.9 degrees C, and the mean treatment time was 34.7 minutes. Ultrasound imaging demonstrated a significant reduction in tumor size (mean, 41%) 5 to 18 days after thermotherapy in 6 (60%) of 10 patients. A significant tumor response on the basis of reduction in tumor size or significant tumor cell kill occurred in 8 (80%) of 10 patients. CONCLUSIONS: With sufficient skin cooling, delivery of focused microwave phased array thermotherapy is safe in treating breast carcinomas when used alone, and some potential efficacy was demonstrated at the tumor thermal doses administered. Increased tumor thermal dose efficacy studies in larger patient populations for improved breast conservation should be investigated.