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1.
Artigo em Inglês | MEDLINE | ID: mdl-31446167

RESUMO

PURPOSE: Methyltetrahydrofolate reductase (MTHFR) C677T (ala222Val) is a single-nucleotide polymorphism (SNP) that affects the formation of 5-methyltetrahydrofolate (5-MTHF), the active folate that allows the recycling of homocysteine (Hcy) to Methionine. Hcy is at the epicentre of oxidative stress and DNA methylation errors. This SNP often increases the circulating Hcy levels and consequently reduces the methylation process, which is involved in the epigenesis and imprinting of markings in gametes. This study aimed to investigate decreases in Hcy levels in MTHFR SNP carriers. PROCEDURE: Eighty-nine couples with fertility problems for at least 3 years were included in this program. The women were systematically tested for the MTHFR C 677T isoform. If the woman tested positive, testing of the male partner was proposed. All the carriers had well-controlled blood Hcy levels before and after treatment (600µg of 5-MTHF/day, with a backup of one carbon cycle during at least 3 months). FINDINGS: As expected, the circulating Hcy level was higher in the homozygous patients than in the heterozygous and wild-type patients. The treatments caused a significant decrease of the circulating Hcy in the SNP carriers group. CONCLUSIONS: Couples with a long history of infertility should be analysed for MTHFR SNP and homocysteine and should be treated with physiological doses of 5-MTHF instead of high doses of folic acid.

2.
Head Neck ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433540

RESUMO

BACKGROUND: Despite advances in treatment, the recurrence rates for laryngeal cancer range from 16% to 40%. METHODS: Patients with recurrent laryngeal cancer treated at Memorial Sloan Kettering (MSK) from 1999 to 2016 were reviewed. Survival outcomes were analyzed. RESULTS: Of 241 patients, 88% were male; the median age was 67 years; 71% had primary glottic tumors. At initial treatment, 72% of patients were seen with early stage disease; primary treatment was radiation (68%), chemoradiation (29%), and surgery (3%). The most common salvage surgery was total laryngectomy (74%). Forty-seven percentage were upstaged at salvage surgery. The 2- and 5-year disease-specific survival (DSS) was 74% and 57%, respectively. Patients with cT4 disease treated with nonsurgical primary management had a 0% 5-year DSS. Independent predictors of DSS were tumor location, perineural invasion, margin, and stage. CONCLUSIONS: Salvage surgery results in acceptable oncologic outcomes. Stage, disease site, perineural invasion, and margins are associated with inferior DSS.

3.
Oral Oncol ; 95: 52-58, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31345394

RESUMO

OBJECTIVE: Polymorphous adenocarcinoma of salivary gland (PAC) is rare. Despite being described as a low risk histology, some patients develop regional and distant metastasis. More aggressive behavior has been attributed to a PAC subcategory called cribriform adenocarcinoma of minor salivary glands (CAMSG). We examined oncological outcomes of PAC. PATIENTS AND METHODS: Fifty-seven patients with PAC were identified from an institutional database of 884 patients surgically treated for salivary gland malignancies from 1985 to 2015. Detailed histopathological analysis was performed. Survival outcomes were calculated using the Kaplan-Meier method. Factors predictive of recurrence were identified using the Cox proportional hazard method. RESULTS: Fifty-four (95%) had tumors of minor salivary gland origin; the most frequent location was the oral cavity in 41 (76%), specifically the hard palate in 32 (55%). Forty-six patients (81%) were clinical T1-T2; 3 (5%) had a clinically positive neck. Thirty-two patients (56%) were classified as PAC and 14 (25%) as CAMSG. Forty-four patients (77%) had surgery alone; 13 (23%) had surgery and postoperative radiotherapy. The 5- and 10-year overall survival and disease-specific survival were 88% and 79% and 98% and 94%, respectively (median follow up 84 [1-159] months); 5- and 10-year recurrence-free survival were 93% and 88%, respectively. Univariate analysis showed male sex, III/IV stage, and CASMG variant had increased incidence of recurrence but were not statistically significant. CONCLUSION: PAC of the salivary glands is an indolent disease with good survival outcomes. Recurrence is uncommon and tends to occur late. Long-term follow-up is indicated in patients with this disease.

4.
Am J Hypertens ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31350541

RESUMO

BACKGROUND: Clinic-based blood pressure (BP) is a closely-tracked metric of healthcare quality, but is prone to inaccuracy and measurement imprecision. Recent guidelines have advocated for automatic office-based BP (AOBP) devices to improve clinic-based BP assessments. METHODS: Patients from a single hypertension clinic underwent a 3-day evaluation that included a 24-hour ambulatory BP monitor (ABPM), two manual clinic-based BP measurements (over two visits), and an unattended AOBP measurement (single visit). All measurements were compared to the average wake-time systolic BP (SBP) and diastolic BP (DBP) from ABPM. RESULTS: Among 103 patients (mean age 57.3±14.8 years, 51% women, 29% black) the average wake-time SBP was 131.3±12.3 mmHg and DBP was 78.3±9.2 mmHg. The average of two manual BPs was significantly higher than wake-time ABPM with mean differences of 5.5 mmHg (P<0.001) for SBP and 2.7 mmHg (P=0.002) for DBP. In contrast, the averages of the last 2 AOBP measurements did not significantly differ from ABPM with mean differences of 1.6 mm Hg (P=0.21) for SBP and -0.5 mm Hg (P=0.62) for DBP. The estimated prevalence of SBP≥140 or DBP≥90 mmHg based on wake-time ABPM was 27.2% versus 49.5% based on the average of two manual measurements (difference 22.3%; P<0.001) and 31.1% based on the average of the last two AOBP measurements (difference 3.9%; P=0.57). CONCLUSIONS: A single visit, unattended AOBP more precisely estimated BP and the prevalence of stage 2 and uncontrolled hypertension than even the average of 2 manual clinic visits, supporting guideline recommendations to use AOBP for clinic-based BP measurements.

5.
Head Neck ; 41(10): 3551-3563, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31294897

RESUMO

BACKGROUND: Timely postoperative radiation therapy (RT) within 50 days of surgery for head and neck cancers provides a survival advantage. METHODS: Using the National Cancer Database, we performed a propensity score-matched analysis comparing patients undergoing open or endoscopic surgery for squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses from 2010 to 2015. RESULTS: Among 168 pairs, patients undergoing endoscopic surgery had shorter time to surgery (24.2 vs 36.7 days, P < .001) and shorter postoperative time to RT (PTTR, 51.2 vs 58.4 days, P = .02). On multivariable linear regression, endoscopic surgery predicted shorter PTTR (ß = -7.6, P = .01). Using the Kaplan-Meier method, patients in the longest PTTR quartile had decreased overall survival (OS; Q1 vs Q4, 3-year OS 76.5% vs 53.3%, P = .007), a durable finding when adjusted for covariates (Q1 vs Q4, HR 0.50, P = .008). CONCLUSIONS: Patients undergoing endoscopic surgery for sinonasal SCC experience shorter PTTR. Shorter PTTR is associated with extended OS.

6.
Innovations (Phila) ; : 1556984519864080, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31354084

RESUMO

OBJECTIVE: The transapical (TA) approach is an alternative access technique for transcatheter aortic valve replacement (TAVR) in patients with symptomatic aortic valve stenosis. The impact of prior coronary artery bypass graft (CABG) surgery and how it affects left ventricular function recovery is not well defined. METHODS: Patients who had TAVR at a single center between June 2012 and December 2016 were reviewed. High-risk patients who underwent the procedure via a TA approach were divided into 2 groups based on their history of CABG surgery. Postoperative outcomes were compared between groups. CABG/TA-TAVR patients were subdivided into 2 per baseline left ventricular ejection fraction (LVEF) <50%. The changes in LVEF and valve function at follow-up (1 to 12 months) were analyzed using paired t-tests. RESULTS: Of 923 cases in total, 183 (19.8%) were performed via a TA approach. The mean ± SD Society of Thoracic Surgeons risk score of TA patients was 10.2 ± 4.6. Forty-nine (27%) had a surgical history of CABG. Overall all-cause mortality rates at 30 days, 1 year, and 2 years were similar for both groups (P = 0.59, P = 0.64, P = 0.78). Subgrouping of CABG-TAVR patients (n = 49) identified 24 patients (49%) with LVEF ≥50% vs. 25 (51%) with LVEF <50%. At 1-year follow-up, significant improvements in LVEF (low LVEF group) and valve function for both groups were observed. LVEF ≥50% group (LVEF: ∆: -3%, P = 0.878; aortic valve area [AVA]: ∆: 1.3 cm2, P < 0.001; mean gradient: ∆: -38 mmHg, P < 0.001); LVEF <50% group (LVEF: ∆: 10%, P = 0.01; AVA: ∆: 1.3 cm2, P < 0.001; MG: ∆: -31 mmHg, P < 0.001). CONCLUSIONS: TA-TAVR can be safely performed with acceptable postoperative outcomes in patients with a history of CABG surgery. In those with reduced EF, significant improvements in LV and valve functions are seen at 1-year follow-up.

7.
J Dermatolog Treat ; : 1-7, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31259638

RESUMO

Sea urchin injuries (SUIs) are among the most common marine injuries; however, there are no guidelines to dictate appropriate workup and treatment. Complications vary significantly depending on the extent of injury, site of injury and elapsed time to medical attention. Timely and appropriate management can prevent long-term morbidity despite the deceptively innocuous appearance of these injuries. We review the English literature on SUIs and offer an algorithm to aid in the management of affected patients. We found that superficially retained spines may trigger a local granulomatous inflammatory response, while spines retained near deep structures may induce sea urchin arthritis, inflammatory tenosynovitis, among other delayed complications. Therefore, we recommend immediate inactivation of pro-inflammatory compounds by hot water soaks at the time of injury, followed by extraction of all spines by a physician. Imaging is a valuable component of risk stratification to determine depth and location of spines, which guides selection of appropriate extraction technique to prevent long-term morbidity.

8.
Oral Oncol ; 94: 86-92, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178218

RESUMO

OBJECTIVE: Previous population-based studies in salivary gland carcinomas have described a relationship between female sex and superior oncological outcome. PATIENTS AND METHODS: Our institutional database of 884 surgically treated patients with salivary gland malignancies from 1985 to 2015 was analyzed for the impact of sex on oncological outcomes. Histologies were classified in three risk groups, low, intermediate and high. Survival outcomes were determined using the Kaplan-Meier method. Hazard ratios for male sex were determined using the Cox proportional hazards model. RESULTS: Eight hundred sixty-seven patients were identified; median age was 59 years, and 51% had a minor salivary gland malignancy. Female patients were younger (58 versus 60 years; p = 0.040) and had a lower incidence of high-risk histologies (25% versus 40%, p < 0.001) and T3-T4 tumors compared to men (23% versus 31%, p < 0.001). With a median follow-up of 57 months, female patients had a superior 5-year disease-specific survival (DSS) (90% versus 79%; p < 0.001). The unadjusted hazard ratio showed male patients had a 2.15-fold increased risk of death (HR 2.15; 95% CI, 1.50-3.06, p < 0.001). After adjusting for Charlson comorbidity index, tobacco use, histological risk group, and overall pathological stage, males still had a statistically significant increased risk of death (HR 1.48; 95% CI 1.05-2.17; p = 0.047). Subgroup analysis showed DSS for females was significantly better in the high-risk histological group (5-year 68% versus 49%, p = 0.007). CONCLUSION: Our study shows that sex has an impact on cancer-specific survival and that female sex favors improved survival.

9.
J Invasive Cardiol ; 31(6): E159, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31158816

RESUMO

Utilization of large-bore sheaths has increased dramatically with the advancement of hemodynamic support devices. The pre-close technique is widely used to achieve hemostasis after device removal. However, this technique might fail or be deferred in certain situations, such as planned extended hemodynamic support or emergencies. Perclose employment in arteriotomies larger than 8 Fr might not be successful, as the device foot does not catch the vessel's anterior wall. We describe a simple "postclose" technique for large arteriotomies (13-14 Fr) after removal of Impella 2.5 or CP systems (Abiomed) from the common femoral artery, using two Perclose devices.

10.
Am J Manag Care ; 25(6): e165-e166, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211547

RESUMO

Medicare's star rating system for Medicare Advantage health plans is a powerful tool for driving plan behavior and, beginning in 2019, CMS is providing new weight to patient access and experience measures. As the shift begins, a recent analysis of person-centered care measures in the star rating system conducted by the Center for Consumer Engagement in Health Innovation found ample room for improving both plan performance and how the ratings measure patient-centeredness. Although from 2010 to 2017, plans performed better on person-centered measures compared with the other measures in the star rating set (3.4 vs 3.0), our analysis also shows that performance on patient-centered measures has not comparatively budged appreciably over time. This may indicate that improvement initiatives focused on non-person-centered star measures have not had a spillover effect on the person-centered measures, or that plans may feel that once a minimum threshold on person-centered measures is met, they need not focus attention on further improvements. At the same time, we need a more comprehensive assessment of person-centeredness. The CMS star measures classified as person-centered are limited in scope and do not constitute a comprehensive view of what it actually means to be person-centered. The new weighting of patient access and experience measures in the CMS star rating system will press plans to refocus their managerial attention, allocate internal assets, and improve their performance, but we also need new measures that are more closely aligned with the domains that describe person-centered care.

11.
Mod Pathol ; 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186531

RESUMO

Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy harboring IDH2 R172 mutations in >80% cases. We explored the potential of genome-wide DNA methylation profiling to elucidate tumor biology and improve the diagnosis of sinonasal undifferentiated carcinoma and its histologic mimics. Forty-two cases, including sinonasal undifferentiated, large cell neuroendocrine, small cell neuroendocrine, and SMARCB1-deficient carcinomas and olfactory neuroblastoma, were profiled by Illumina Infinium Methylation EPIC array interrogating >850,000 CpG sites. The data were analyzed using a custom bioinformatics pipeline. IDH2 mutation status was determined by the targeted exome sequencing (MSK-IMPACTTM) in most cases. H3K27 methylation level was assessed by the immunohistochemistry-based H-score. DNA methylation-based semi-supervised hierarchical clustering analysis segregated IDH2 mutants, mostly sinonasal undifferentiated (n = 10) and large cell neuroendocrine carcinomas (n = 4), from other sinonasal tumors, and formed a single cluster irrespective of the histologic type. t-distributed stochastic neighbor embedding dimensionality reduction analysis showed no overlap between IDH2 mutants, SMARCB1-deficient carcinoma and olfactory neuroblastoma. IDH2 mutants demonstrated a global methylation phenotype and an increase in repressive trimethylation of H3K27 in comparison to IDH2 wild-type tumors (p < 0.001). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed no difference in pathway activation between IDH2-mutated sinonasal undifferentiated and large cell neuroendocrine carcinomas. In comparison to SMARCB1-deficient, IDH2-mutated carcinomas were associated with better disease-free survival (p = 0.034) and lower propensity for lung metastasis (p = 0.002). ARID1A mutations were common in small cell neuroendocrine carcinoma but not among IDH2 mutants (3/3 versus 0/18 and p < 0.001). IDH2 mutations in sinonasal carcinomas induce a hypermethylator phenotype and define a molecular subgroup of tumors arising in this location. IDH2-mutated sinonasal undifferentiated carcinoma and large cell neuroendocrine carcinoma likely represent a phenotypic spectrum of the same entity, which is distinct from small cell neuroendocrine and SMARCB1-deficient sinonasal carcinomas. DNA methylation-based analysis of the sinonasal tumors has potential to improve the diagnostic accuracy and classification of tumors arising in this location.

13.
Complement Ther Med ; 44: 223-234, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126560

RESUMO

OBJECTIVE: Sauna-bathing is an ancient tradition that is gaining popularity across the world as a wellness tool. There is a growing body of medical evidence supporting the role of saunas, or whole-body thermotherapy, as a form of treatment for a range of health issues. However, the demographics, motivations and experiences of current sauna bathers have not yet been explored on a global scale. This study is designed to explore these themes. DESIGN: An online 71-item questionnaire compiling information on the individual characteristics, sauna-related habits and perceived health and wellness experiences of regular sauna bathers was conducted from October 2016 to October 2017. The validated 'SF-12' quality of life scoring tool was incorporated into the questionnaire to measure physical and mental indicators of well-being. RESULTS: Of 572 logins recorded, 482 valid responses were generated. Both men (51.3%) and women (48.7%) were represented, and respondents were predominantly well-educated (81.8%), non-smoking (90.6%), regularly-exercising (78.8%) individuals of normal-to-overweight status (87.1%) who sauna-bathed approximately 1-2 times per week. The key reasons indicated by respondents for sauna-bathing included relaxation/stress reduction, pain relief and socializing. Nearly a third of respondents reported medical conditions and of this subset, those with back/musculoskeletal pain and mental issues cited the greatest improvements in their conditions with sauna-bathing. Of all respondents, 83.5% reported sleep benefits after sauna use. Analysis of well-being scores after stratifying respondents into three groups by sauna-bathing frequency (group I: <5 times per month; group II: 5-15 times per month; group III: >15 times per month) revealed group II respondents had slightly higher mental well-being scores (Kruskal-Wallis testing: H = 6.603 > ꭔ2 of 5.991, p = 0.0368, df = 2 with post hoc analysis using Mann-Whitney U test: p = 0.016) as compared to respondents who were sauna-bathing less frequently (group I). No respective differences were detected between the physical well-being scores of any of the three groups. Adverse reactions to sauna-bathing were recorded as mostly minor (93.1%), including primarily symptoms of dizziness, dehydration and headache. However, there were two reports (0.3%) of chest pain and eye irritation requiring hospitalization. CONCLUSIONS: This cross-sectional study documents that sauna-bathing participants, particularly those from Finland, Australia and the United States, are motivated to use saunas predominantly for relaxation, reporting health benefits especially around mental well-being and sleep, with relatively few adverse effects. While these results reinforce some of the known health benefits of sauna bathing, they indicate that further research and better dissemination of existing evidence is needed to fully develop the sauna's potential as a therapeutic intervention.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31078438

RESUMO

BACKGROUND: Patients with type 2 myocardial infarction (MI) are often classified under the diagnosis of non-ST-segment-elevation MI (NSTEMI) despite the significant differences in clinical characteristics, management, and outcomes between type 2 MI and type 1 NSTEMI. This may have significant implications that can lead to inaccurate assessment of quality measures by MI quality review programs. METHODS: A single-center retrospective study of 1224 patients discharged with the diagnosis of type 1 NSTEMI between January 2015 and September 2017. Based on the third universal definition of MI, we stratified patients into type 2 MI or type 1 NSTEMI. Patient's characteristics, comorbidities, medications prescribed during hospitalization and at discharge, readmissions within 30 days after discharge, and diagnostic and therapeutic interventions data was collected. The primary goal of this study was to identify how often type 2 MI patients were misclassified as type 1 NSTEMI, we also assessed the differences in treatment and outcomes between type 2 MI and type 1 NSTEMI. RESULTS: 1224 patients assigned the ICD-9 and ICD-10 codes of type 1 NSTEMI at discharge were evaluated for study inclusion. After application of the inclusion criteria, 945 patients were included in the final analysis. Of these 945 patients, 281 (29.7%) patients were classified as type 2 MI and 664 (70.3%) patients were classified as type 1 NSTEMI. Patients with type 2 MI were older, more likely to have systolic heart failure, had lower peak troponin levels, were less likely to receive aspirin, P2Y12 inhibitors and statin at discharge, and had longer length of stay. Compared with type 1 NSTEMI patients, those with type 2 MI had higher all cause 30-day mortality (13.5% versus 2.9%, P < 0.0001) (RR: 4.65; 95% CI, 2.85-9.65). After adjusting for patient demographics, comorbidities, and medications, patients with type 2 MI were still more likely to die within 30 days after discharge (RR: 2.89; 95% CI, 1.58-7.46). In addition, patients with type 2 MI were more likely to be readmitted within 30 days after discharge than patients with type 1 NSTEMI (17.7% versus 13.9%, P < 0.01) (RR: 1.27; 95% CI, 1.08-2.5). CONCLUSIONS: Close to one third of patients given the diagnosis of type 1 NSTEMI at discharge at our institution were type 2 MI patients. Patients with type 2 MI are managed differently from type 1 NSTEMI patients and have higher 30-day mortality and readmission rate. Misclassification of type 2 MI as type 1 NSTEMI can have a significant impact on hospitals MI clinical performance and quality measures.

15.
Catheter Cardiovasc Interv ; 94(2): 243-248, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132218

RESUMO

OBJECTIVES: To assess the safety and feasibility of percutaneous transaxillary (TAx) access for peripheral endovascular interventions. BACKGROUND: The common femoral artery (CFA) is the most commonly used access site for peripheral endovascular interventions. However, its use might be precluded in multiple circumstances. The axillary artery is comparable in size to the CFA and is less affected by atherosclerosis. Data regarding its percutaneous use in peripheral endovascular interventions are scarce. METHODS: Consecutive patients who underwent percutaneous TAx peripheral endovascular interventions were identified. Demographic and periprocedural data were extracted. Axillary artery access was obtained percutaneously with the arm abducted. A destination sheath was advanced to the relevant vessel. Endovascular interventions were performed using standard devices and techniques. Vascular closure devices were utilized to achieve hemostasis. Primary endpoints included procedural technical success, access-related complications, and major adverse events (MAEs). Secondary endpoints included cannulation time, total procedure time, fluoroscopy time, and length of stay (LOS). RESULTS: Percutaneous TAx access was successfully utilized to perform 41 procedures in 29 patients, lacking a suitable conventional access. Three quarters of target vessels were infrainguinal. The lesions of 61% were classified as TransAtlantic Inter-Society Consensus (TASC) C or D. Access-related complications occurred in two procedures (5%). No MAEs occurred. Median cannulation time was 12 min, procedure time 135 min, fluoroscopy time 20 min, and LOS 1 day. CONCLUSIONS: When no suitable access exists for lower extremity catheter-based interventions, percutaneous TAx approach is a feasible and safe alternative. As such facility with this approach is a valuable asset for interventionalists.

16.
Head Neck ; 41(8): 2741-2747, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30933393

RESUMO

BACKGROUND: Standard treatment of squamous cell carcinoma (SCC) of the anterior nasal mucosa is surgical resection with or without postoperative radiation. METHODS: Retrospective review of patients diagnosed with SCC of the nasal cavity between January 2000 and July 2018 who refused total rhinectomy and who were treated with radiation with or without chemotherapy with curative intent. RESULTS: Eleven patients were identified, 73% had stage III or stage IV disease. Four patients were treated with intensity-modulated radiotherapy and seven with intensity-modulated proton radiotherapy. Concurrent chemoradiotherapy was used in nine patients (82%). With a median follow-up of 15 months (3-124 months), two patients experienced recurrence and one developed distant metastasis and died from disease. The 2-year rhinectomy-free survival rate was 88%. Two-year overall survival and recurrence-free survival were 100% and 75%, respectively. CONCLUSION: A radiation-based approach for SCC of the nasal cavity mucosa is a valid option for selected patients who refuse up-front surgery.

17.
J Invasive Cardiol ; 31(5): 153-158, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31034436

RESUMO

BACKGROUND: The current study aims to identify predictors of extended postoperative length of stay (PLOS) after uncomplicated transcatheter aortic valve replacement (TAVR). METHODS: Patients who underwent TAVR at a single center between June 2012 and June 2016 were analyzed. Patients were stratified by time into an early cohort (EC; 2012-2014) and current cohort (CC; 2015-2016). Those who had complications post procedure were excluded. The CC group was dichotomized based on its median PLOS. Factors associated with a longer PLOS were investigated by using multivariable logistic regression analysis. RESULTS: Mean age of the 686 patients (299 in the EC group and 387 in the CC group) was 82 ± 8 years. PLOS in the CC group was significantly lower than in the EC group (4 days vs 6 days, respectively; P<.001). Median PLOS in the CC group was 2 days. Dichotomizing the CC group by median PLOS resulted in 148 patients (54%) ≤2 days vs 128 patients (46%) >2 days. Of these, PLOS was 1 day in 71 patients (26%) and 2 days in 61 patients (28%). Independent predictors of PLOS >2 days were non-transfemoral approach, non-elective admission, female sex, low mean transaortic gradient, presence of chronic renal failure, and pulmonary hypertension. CONCLUSION: Experience coupled with improvements in TAVR technology over the past few years have led to a significant decrease in PLOS after TAVR. In the current TAVR era, 1 out of every 2 patients stays for a day or two in the absence of perioperative adverse events.

18.
Am J Cardiol ; 124(1): 85-89, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31027658

RESUMO

The study aims to investigate the incidence of immediate renal function improvement in renal dysfunction patients who had transcatheter aortic valve implantation (TAVI). TAVI patients with ≥ moderate reduced renal function [estimated GFR ≤ 60 ml/min/1.73 m2] at baseline were identified from a prospectively maintained database. Patients were divided into 3 groups based on percent change [(discharge eGFR - baseline eGFR/baseline GFR) × 100] in eGFR post-TAVR. Improvement ≥ 10%, no change, Decline ≥ 10%. Multivariable logistic regression was performed to identify factors that predicted improvement/decline in GFR postprocedure. Out of 677 patients, 359 (53%) had eGFR ≤ 60 ml/min/1.73 m2. Of these, 188 (52%) had an improvement in eGFR ≥ 10%, 125 (34%) had no change and 48 (14%) observed decline ≥ 10%. All groups had similar proportions of females and age was comparable in patient groups. Patients in whom a decline in eGFR was observed had significantly higher Society of thoracic Surgeons scores (10.7 vs 8.2 vs 8.2; p = 0.007) and incidence of liver disease (6% vs, 0% vs 2%; p = 0.014) than the no-change or improved groups respectively. On multivariable analysis, independent predictors of decline/improvement in eGFR were being female, low left ventricular ejection fraction and baseline liver dysfunction. In conclusion, over half of patients with compromised renal function who underwent TAVI experience an immediate improvement in kidney function post-TAVI. Being female, baseline liver dysfunction and a low left ventricular ejection fraction is associated with an immediate decline in eGFR.

19.
Nat Med ; 25(5): 767-775, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31011208

RESUMO

Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.


Assuntos
Antígenos de Neoplasias/genética , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/imunologia , Fusão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/imunologia , Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/imunologia , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Sequenciamento Completo do Genoma
20.
Crit Rev Food Sci Nutr ; : 1-12, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31032630

RESUMO

The health benefits of long-term dietary plant ingestion are well-established. However, literature on acute nutritional challenges is very limited. This study aimed to identify available evidence on transcriptomics responses to acute ingestion of plants or plant extracts and identify signature gene profiles that may serve as biomarkers of health status. We systematically searched electronic databases and extracted information based-on inclusion criteria such as human clinical studies, single plant-based nutrients and outcomes reported on acute transcriptome responses. A total of 11 studies reported on acute intake of plant dietary interventions. Four studies investigating natural oil extracts with three reporting on whole plants and two studies on natural plant-derived extracts. Gene expression was found to be associated with immune response (7 studies), inflammation (9 studies), metabolism (8 studies), cellular processes and cancer. The finding of this systematic review suggests that acute ingestion may significantly impact diverse physiological and pathological pathways including inflammatory, immune, cancer and oxidative stress pathways. Transcriptomics approach is proven to be an effective strategy in discovery of these anticipated mechanisms. Further studies are now required to validate and continue exploring the short-term health impact of dietary plants and their bioactive phytochemicals on gene expression and function.

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