Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.078
Filtrar
1.
Urology ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32413517

RESUMO

OBJECTIVES: To better understand the financial implications of readmission after radical cystectomy, an expensive surgery coupled with a high readmission rate. Currently, whether hospitals benefit financially from readmissions after radical cystectomy remains unclear, and potentially obscures incentives to invest in readmission reduction efforts. METHODS: Using a 20% sample of national Medicare beneficiaries, we identified 3,544 patients undergoing radical cystectomy from January 2010 to November 2014. We compared price-standardized Medicare payments for index admissions and readmissions after surgery. We also examined the variable financial impact of length of stay and the proportion of Medicare payments coming from readmissions based on overall readmission rate. RESULTS: Medicare patients readmitted after cystectomy had higher index hospitalization payments ($19,164 readmitted vs. $18,146 non-readmitted, p=0.03) and an average readmission payment of $7,356. Adjusted average Medicare readmission payments and length of stay varied significantly across hospitals, ranging from $2,854 to $15,605, and 2.0 to 17.1 days, respectively (both p<0.01), with longer length of stay associated with increased payments. After hospitals were divided into quartiles based on overall readmission rates, the percent of payments coming from readmissions ranged from 5% to 13%. CONCLUSIONS: Readmissions following radical cystectomy were associated with increased Medicare payments for the index hospitalization, and the readmission payment, potentially limiting incentives for readmission reduction programs. Our findings highlight opportunities to reframe efforts to support patients, caregivers, and providers through improving the discharge and readmission processes to create a patient-centered experience, rather than for fear of financial penalties.

2.
PLoS Genet ; 16(4): e1008728, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32352966

RESUMO

Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with tuberculosis (TB) risk. However, neither explains a large portion of disease risk or severity. Based on studies in other infectious diseases and animal models of TB, we hypothesized that the genomes of the two interact to modulate risk of developing active TB or increasing the severity of disease, when present. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which there were 3 MTB lineages of which L4-Ugandan (L4.6) is the most recent. TB severity, measured using the Bandim TBscore, was modeled as a function of host SNP genotype, MTB lineage, and their interaction, within two independent cohorts of TB cases, N = 113 and 121. No association was found between lineage and severity, but association between multiple polymorphisms in IL12B and TBscore was replicated in two independent cohorts (most significant rs3212227, combined p = 0.0006), supporting previous associations of IL12B with TB susceptibility. We also observed significant interaction between a single nucleotide polymorphism (SNP) in SLC11A1 and the L4-Ugandan lineage in both cohorts (rs17235409, meta p = 0.0002). Interestingly, the presence of the L4-Uganda lineage in the presence of the ancestral human allele associated with more severe disease. These findings demonstrate that IL12B is associated with severity of TB in addition to susceptibility, and that the association between TB severity and human genetics can be due to an interaction between genes in the two species, consistent with host-pathogen coevolution in TB.

3.
J Phys Chem B ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396356

RESUMO

Serine side-chains are strategic sites of post-translational modifications and it is important to establish benchmarks of their internal dynamics. In this work we compare the dynamics of serine side-chains in several biologically important systems: Serine-8 in the disordered domain of Aß(1-40) fibrils in the hydrated and dry states and fluorenylmethyloxycarbonyl(Fmoc) serine with the bulky group that mimics hydrophobicity of the fibrils contacts yet lacks the complexity of the protein system. Using deuterium solid-state NMR static line shape and longitudinal relaxation techniques in the 310 to 180 K temperature range, we compare the main features of the dynamics in these systems. The main motional modes in the fibrils are large-scale fluctuations in the hydrated state of the fibrils, as well as local motions such as 3-site jumps of the Cßdeuterons at high temperatures and small-angle fluctuations of the Cα-Cß axis at low temperatures. In the hydrated fibrils two distinct states are present with vastly different extent of large scale diffusive motions and 3-site jumps rate constants. The hydrated state at the physiological conditions is dominated by the "free" state undergoing large-scale diffusive motions and very fast local 3-site jumps, while in the "bound" state these large scale motions are quenched due to transient inter- and intra-molecular interactions. Additionally, in the bound state the 3-site jumps motions are orders of magnitude slower. Details of the dynamics in the serine side-chain are dependent on fine structural features and hydration levels of the systems.

4.
Arthroscopy ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32353622

RESUMO

PURPOSE: To evaluate outcome data of patients undergoing DeJour sulcus-deepening trochleoplasty with medial patellofemoral ligament reconstruction (MPFLR) for high-grade trochlear dysplasia at a single institution in the United States. METHODS: A total of 67 patients (76 knees) with severe trochlear dysplasia and recurrent patellar instability were prospectively enrolled and underwent DeJour sulcus-deepening trochleoplasty with MPFLR from 2011-2019. Inclusion criteria included recurrent lateral patellar instability following failure of conservative treatment with radiographic evidence of severe trochlear dysplasia (DeJour types B or D). Patients were excluded with less than 2-year follow-up. Radiographic analysis, physical examination, clinical follow-up, patient demographics, and patient reported outcome measures were obtained for all patients at each visit. RESULTS: Forty patients (44 knees) had complete two-year or longer follow-up and were included. The majority of patients were female (81.8%) with a mean age of 19.2 years (SD 6.7; range 13.2-47.0). Follow-up ranged from 2.0 years to 6.8 years (mean 3.6 years, SD 1.35). 45.5% had failed prior surgery for patellar instability. Eight knees developed arthrofibrosis and the overall reoperation rate was 27.3%. No patients had fixation failure and no further surgery was required for instability. The mean preoperative IKDC score of 50.8 improved to 79.1 (p < 0.001) and the mean preoperative Kujala score of 56.4 improved to 86.5 (p < 0.001). Patients reported high satisfaction rates (mean 9.1 out of 10). When applicable, 100% of patients returned to work while 84.8% returned to sport. There was no significant radiographic progression of patellofemoral arthritis at a mean of 2.4 years after surgery (SD 1.7). CONCLUSIONS: DeJour sulcus-deepening trochleoplasty combined with MPFLR and used with tibial tubercle osteotomy and lateral release is a reliable and effective treatment for recurrent patellar instability due to severe trochlear dysplasia, even in this group with many revisions of prior procedures.

5.
Nat Commun ; 11(1): 2135, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358509

RESUMO

A non-immunogenic tumor microenvironment (TME) is a significant barrier to immune checkpoint blockade (ICB) response. The impact of Polybromo-1 (PBRM1) on TME and response to ICB in renal cell carcinoma (RCC) remains to be resolved. Here we show that PBRM1/Pbrm1 deficiency reduces the binding of brahma-related gene 1 (BRG1) to the IFNγ receptor 2 (Ifngr2) promoter, decreasing STAT1 phosphorylation and the subsequent expression of IFNγ target genes. An analysis of 3 independent patient cohorts and of murine pre-clinical models reveals that PBRM1 loss is associated with a less immunogenic TME and upregulated angiogenesis. Pbrm1 deficient Renca subcutaneous tumors in mice are more resistance to ICB, and a retrospective analysis of the IMmotion150 RCC study also suggests that PBRM1 mutation reduces benefit from ICB. Our study sheds light on the influence of PBRM1 mutations on IFNγ-STAT1 signaling and TME, and can inform additional preclinical and clinical studies in RCC.

6.
Am J Hum Genet ; 106(5): 587-595, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32359473

RESUMO

Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively "autism-specific" genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research. We argue that there is currently insufficient evidence to establish meaningful ASD specificity of any genes based on large-effect rare-variant data.

7.
Hum Mol Genet ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32412639

RESUMO

Prostate cancer is the second leading cause of male cancer death in the United States. The androgen receptor (AR) transcription factor is a master regulator of normal glandular homeostasis in the prostate, as well as growth and survival of prostate cancer cells. Therefore, AR-targeted therapies are effective for improving overall survival of patients with advanced prostate cancer that is incurable by surgery or radiation. However, prostate cancer will inevitably progress on AR-targeted therapies to a castration-resistant prostate cancer (CRPC) phenotype that accounts for virtually all prostate cancer-specific death. mRNA transcript variants of the AR gene are expressed in CRPC cells, and can be translated to produce AR variant (AR-V) proteins that function as ligand-independent, constitutively active transcription factors. AR-Vs are able to support growth of CRPC cells by promoting expression of AR target genes that are normally suppressed by AR-targeted therapies. Knowledge of mechanisms that govern expression of AR-Vs is incomplete. Studies have shown genomic rearrangements of the AR gene underlie expression of diverse AR-Vs in certain CRPC tumors, but post-transcriptional processes represent a broader regulatory mechanism for expression of AR-Vs in CRPC. This review focuses on alternative splicing, 3' end processing, and miRNA-mediated mRNA repression of AR and AR-V expression, and the potential these mechanisms hold as therapeutic targets for CRPC.

8.
Res Social Adm Pharm ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32409150

RESUMO

BACKGROUND: Chloroquine or hydroxychloroquine (chloroquine) plus azithromycin is considered as therapy for COVID-19. With benefit evaluations underway, safety concerns due to potential additive effects on QTc prolongation should be addressed. OBJECTIVE: We compared risk of cardiac adverse events between combinations of chloroquine and azithromycin and chloroquine and amoxicillin. METHODS: We conducted a retrospective cohort study using the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, 2005-2018. We included autoimmune disease patients aged ≥18 years initiating azithromycin or amoxicillin for ≥5 days during chloroquine treatment. Patients had continuous insurance coverage ≥6 months before combination use until 5 days thereafter or inpatient death. Two outcomes were sudden cardiac arrest/ventricular arrhythmias (SCA/VA) and cardiac symptoms. We followed patients for up to 5 days to estimate hazard ratios (HR). Covariates were adjusted using stabilized inverse probability treatment weighting. RESULTS: We identified two SVC/VA events among >145,000 combination users. The adjusted incidence of cardiac symptoms among azithromycin and amoxicillin users was 276 vs 254 per 10,000 person-years with an adjusted HR of 1.10 (95%CI, 0.62-1.95). CONCLUSION: Combination use of chloroquine and azithromycin at routine doses did not show pronounced increases in arrhythmias in this real-world population, though small sample size and outcome rates limit conclusions.

9.
Nat Commun ; 11(1): 2444, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415068

RESUMO

The essential role of ORAI1 channels in receptor-evoked Ca2+ signaling is well understood, yet little is known about the physiological activation of the ORAI channel trio natively expressed in all cells. The roles of ORAI2 and ORAI3 have remained obscure. We show that ORAI2 and ORAI3 channels play a critical role in mediating the regenerative Ca2+ oscillations induced by physiological receptor activation, yet ORAI1 is dispensable in generation of oscillations. We reveal that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca2+ signals, reflecting their enhanced basal STIM1-binding and heightened Ca2+-dependent inactivation. This broadened bandwidth of Ca2+ influx is translated by cells into differential activation of NFAT1 and NFAT4 isoforms. Our results uncover a long-sought role for ORAI2 and ORAI3, revealing an intricate control mechanism whereby heteromerization of ORAI channels mediates graded Ca2+ signals that extend the agonist-sensitivity to fine-tune transcriptional control.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32417044

RESUMO

BACKGROUND: Many options exist for reconstructing the shoulder after large bony resections of the proximal humerus. One of the more widely used is endoprosthetic replacement. Proximal migration of unconstrained hemiarthroplasty articulations may cause difficulties particularly in the setting of loss of the rotator cuff and/or deltoid musculature. To attempt to overcome these issues, a fixed-fulcrum constrained reverse shoulder replacement option may be considered. METHODS: A retrospective review of prospectively collected data from the Queensland Bone and Soft Tissue Sarcoma Service was undertaken to compare the function, implant survivorship, and reoperation rate of constrained reverse and unconstrained hemiarthroplasty-type endoprostheses in patients with tumors. RESULTS: We retrospectively reviewed data on 41 consecutive proximal or total humeral endoprosthetic replacements undertaken between January 2003 and July 2018. One patient was excluded as lost to follow-up prior to 24 months. There were 21 unconstrained implants and 19 constrained shoulder replacements (Stanmore Modular Endoprosthesis Tumour System with Bayley-Walker articulation). Proximal migration of the unconstrained hemiarthroplasty articulation occurred in 8 patients (38%), and dislocation or failure of the constrained mechanism occurred in 5 (26%). Reoperation for implant-related issues was required in 5 patients in the constrained group and none in the unconstrained group. Of the 18 patients alive at the time of review, 12 provided functional scores. The mean follow-up period for surviving patients was 4.2 years (standard deviation, 2.7 years), with a minimum of 2 years' follow-up. Functional scores were similar between the 2 groups. CONCLUSION: Constrained reverse prostheses were associated with a higher reoperation rate in this series without any functional benefit compared with unconstrained hemiarthroplasty-type articulations. We favor the use of unconstrained hemiarthroplasty-type endoprostheses for reconstruction after resection of destructive lesions of the proximal humerus.

11.
J Bone Joint Surg Am ; 102(9): 778-787, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32379118

RESUMO

BACKGROUND: There is no consensus whether the interim antibiotic spacer utilized in the 2-stage exchange arthroplasty should immobilize the joint or allow for motion. The purpose of this multicenter, randomized clinical trial was to compare static and articulating spacers as part of the 2-stage exchange arthroplasty for the treatment of chronic periprosthetic joint infection complicating total knee arthroplasty as defined with use of Musculoskeletal Infection Society criteria. METHODS: Sixty-eight patients undergoing 2-stage exchange arthroplasty were randomized to either a static (32 patients) or an articulating (36 patients) spacer. An a priori power analysis determined that 28 patients per group would be necessary to detect a 13° difference in range of motion between groups. Six patients were excluded after randomization, 6 died, and 7 were lost to follow-up before 2 years. RESULTS: Patients in the static group had a hospital length of stay that was 1 day greater than the articulating group after stage 1 (6.1 compared with 5.1 days; 95% confidence interval [CI], 5.3 to 6.9 days and 4.6 to 5.6 days, respectively; p = 0.032); no other differences were noted perioperatively. At a mean of 3.5 years (range, 2.0 to 6.4 years), 49 patients were available for evaluation. The mean motion arc was 113.0° (95% CI, 108.4° to 117.6°) in the articulating spacer group, compared with 100.2° (95% CI, 94.2° to 106.1°) in the static spacer group (p = 0.001). The mean Knee Society Score was higher in the articulating spacer cohort (79.4 compared with 69.8 points; 95% CI, 72.4 to 86.3 and 63.6 to 76.1, respectively; p = 0.043). Although not significantly different with the sample size studied, static spacers were associated with a greater need for an extensile exposure at the time of reimplantation (16.7% compared with 4.0%; 95% CI, 0.6% to 38.9% and 0.5% to 26.3%, respectively; p = 0.189) and a higher rate of reoperation (25.0% compared with 8.0%; 95% CI, 9.8% to 46.7% and 1.0% to 26.0%, respectively; p = 0.138). CONCLUSIONS: Articulating spacers provided significantly greater range of motion and higher Knee Society scores at a mean of 3.5 years. Static spacers were associated with a longer hospital stay following removal of the infected implant. When the soft-tissue envelope allows and if there is adequate osseous support, an articulating spacer is associated with improved outcomes. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32379979

RESUMO

RATIONALE: Acute rejection, manifest as lymphocytic inflammation in a perivascular (acute perivascular rejection, AR) or peribronchiolar (lymphocytic bronchiolitis, LB) distribution, is common in lung transplant recipients and increases the risk for chronic graft dysfunction. OBJECTIVES: Evaluate clinical factors associated with biopsy proven acute rejection during the first posttransplant year in a present-day, five-center lung transplant cohort. METHODS: We analyzed prospective diagnoses of AR and LB from over 2,000 lung biopsies in 400 newly transplanted adult lung recipients. Because LB without simultaneous AR was rare, our analyses focused on risk factors for AR. Multivariable Cox proportional hazards models were used to assess donor and recipient factors associated with the time to first AR occurrence. MEASUREMENTS AND MAIN RESULTS: 53.3% of patients experienced at least one AR episode during the first posttransplant year. Multivariable proportional hazards analyses accounting for enrolling center effects identified four or greater HLA mismatches (HR 2.06, p=<0.01) as associated with increased AR hazards, while bilateral transplantation (HR 0.57, p=<0.01) was associated with protection from AR. Additionally, Wilcoxon rank-sum analyses demonstrated bilateral (vs. single) lung recipients and those with fewer than 4 (vs greater than 4) HLA mismatches demonstrated reduced AR frequency and/or severity during the first posttransplant year. CONCLUSIONS: We found a high incidence of AR in a contemporary multicenter lung transplant cohort undergoing consistent biopsy sampling. While not previously recognized, the finding of reduced AR in bilateral lung recipients is intriguing, warranting replication and mechanistic exploration.

13.
Spine Deform ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32383143

RESUMO

STUDY DESIGN: It is a retrospective cohort study. OBJECTIVES: To compare the radiographic and clinical outcomes of serial body casting for infantile idiopathic scoliosis (IIS) with versus without the use of general anesthesia (GA). Serial body casting for IIS has traditionally been performed under GA. However, reports of neurotoxic effects of anesthetics in young children have prompted physicians to consider instead performing these procedures while patients are awake and distracted by electronic devices. METHODS: Patients from a multicenter registry who underwent serial casting for IIS were included. The patients were divided into asleep (GA) and awake (no GA) cohorts. Comparisons were made between pre-casting, first in-cast, and post-casting radiographic measures in each cohort. The rates of successful casting (≥ 10° major CA improvement), curve progression, and incidence of casting abandonment for surgical intervention were also compared. RESULTS: One-hundred and twenty-one patients who underwent serial casting for IIS were included. Ninety-two (76%) patients were asleep during casting procedures, while 29 (24%) were awake. Patients in the awake cohort were older (p < 0.01), had a lower BMI (p = 0.03), and more severe curve magnitudes (p < 0.01) at baseline. Patients in the awake cohort experienced greater first-in-cast correction of the major curve (p = 0.01) and improvement in thoracic spine height (p < 0.01). The rate of casting success was higher in the awake cohort (72%) as compared to the asleep cohort (48%) (p = 0.02), although the rate of curve progression (worsening) was similar (p = 0.880). Lastly, there was a lower rate of conversion to surgery at 2 years post-initiation of casting, although this was not statistically significant (0% vs. 8%; p = 0.126). CONCLUSIONS: Patients who underwent awake serial casting had similar radiographic outcomes as compared to those who were under general anesthesia during the procedures. Thus, awake casting may provide a safe and effective alternative to the use of general anesthesia in patients with idiopathic infantile scoliosis. LEVEL OF EVIDENCE: III.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32437922

RESUMO

PURPOSE: Ewing sarcoma of the pelvis is associated with inferior local control compared to those arising from other primary sites. Despite its increased use, outcome data for treatment with proton therapy remain limited. We report 3-year disease control and toxicity in pediatric patients treated with proton therapy. METHODS: Thirty-five patients aged ≤21 years (median, 14 years) with non-metastatic pelvic Ewing sarcoma received proton therapy and chemotherapy between 2010 and 2018. Overall survival and tumor control rates were calculated using the Kaplan-Meier method. A log-rank test assessed significance between strata of prognostic factors. Significant toxicity was reported per CTCAE, version 4.0. RESULTS: Most patients received definitive radiation (n=26; median dose 55.8GyRBE [range 54-64.8]), 7 received preoperative radiation (50.4 GyRBE), and 2 received postoperative radiation (45 GyRBE and 54GyRBE). The median primary tumor size was 10.5 cm. With a median follow-up of 3 years (range, 0.3-9.0 years), the 3-year overall survival, progression-free survival, and local control rates were 83% (95% CI 65-93%), 64% (95% CI 45-79%), and 92% (95% CI 74-98%), respectively. There was no association between LC, PFS, or OS and tumor size, patient age, radiation dose, or definitive versus pre-/postoperative radiotherapy. Median time to progression was 1 year (range, 0.1-1.9 years). All patients with large tumors (≥8 cm) who underwent definitive proton therapy with a higher dose (≥59.4 Gy RBE) remained free from tumor recurrence (n=5). Five patients experienced grade ≥2 subacute/late toxicity, all of whom were treated with combined surgery and radiation. CONCLUSION: Definitive proton therapy offers local control comparable to photon therapy in pediatric patients with pelvic Ewing sarcoma. These data lend preliminary support to radiation dose escalation without significant toxicity, which may contribute to the favorable outcomes. Combined surgery and radiotherapy, particularly preoperative radiation, is associated with postoperative complications, but not survival, compared to radiation alone.

15.
Cancer Invest ; : 1-14, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441531

RESUMO

BACKGROUND: Meningiomas represent ∼30% of primary central nervous system (CNS) tumors. Although advances in surgery and radiotherapy have significantly improved survival, there remains an important subset of patients whose tumors have more aggressive behavior and are refractory to conventional therapy. Recent advances in molecular genetics and epigenetics suggest that this aggressive behavior may be due to the deletion of the DNA repair and tumor suppressor gene, CHEK2, neurofibromatosis Type 2 (NF2) mutation on chromosome 22q12, and genetic abnormalities in multiple RTKs including FGFRs. Management of higher-grade meningiomas, such as anaplastic meningiomas (WHO grade III), is truly challenging and there isn't an established chemotherapy option. We investigate the effect of active multi tyrosine receptor kinase inhibitor Dovitinib at stopping AM cell growth in in vitro with either frequent codeletion or mutated CHEK2 and NF2 gene.METHODS: Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot analysis, caspases assay, and DNA fragmentation assay.RESULTS: Treatment of CH157MN and IOMM-Lee cells with Dovitinib suppressed multiple angiokinases - mainly FGFRs, leading to suppression of downstream signaling by RAS-RAF-MAPK molecules and PI3K-AKT molecules which are involved in cell proliferation, cell survival, and tumor invasion. Furthermore, Dovitinib induced apoptosis via downregulation of survival proteins (Bcl-XL), and over-expression of apoptotic factors (Bax and caspase-3) regardless of CHEK2 and NF2 mutation status.CONCLUSIONS: This study establishes the groundwork for development of Dovitinib as a therapeutic agent for high-grade AM with either frequent codeletion or mutated CHEK2 and NF2, an avenue with high translational potential.

16.
J Thromb Haemost ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433797

RESUMO

BACKGROUND: A previous individual participant data (IPD) meta-analysis showed that the Wells-rule and D-dimer testing cannot exclude suspected deep vein thrombosis (DVT) in cancer patients. OBJECTIVES: To explore reasons for this reduced diagnostic accuracy and to optimize the diagnostic pathway for cancer patients suspected of DVT. PATIENTS AND METHODS: Using IPD from 13 studies in patients with suspected DVT, DVT prevalence and the predictive value of the Wells-rule items and D-dimer testing were compared between patients with and without cancer. Next, we developed a prediction model with five variables selected from all available diagnostic predictors. RESULTS: Among the 10,002 suspected DVT patients, there were 834 patients with cancer. The median prevalence of DVT in these patients with cancer was 37.5% (interquartile range [IQR] 30.8-45.5), while it was 15.1% (IQR 11.5-16.7) in patients without cancer. Diagnostic performance of individual Wells-rule items and D-dimer testing was similar across patients with and without cancer, except 'immobility' and 'history of DVT'. The newly developed rule showed a pooled c-statistic 0.80 (95% confidence interval [CI] 0.75-0.83) and good calibration. However, using this model, still only 4.3% (95% CI 3.0-5.7) of the suspected patients with cancer could be identified with a predicted DVT post-test probability of less than 2%. CONCLUSIONS: Likely due to the high prevalence of DVT, clinical models followed by D-dimer testing fail to rule-out DVT efficiently in cancer patients suspected of DVT. Direct referral for compression ultrasonography appears to be the preferred approach for diagnosis of suspected DVT in cancer patients.

17.
BMC Med Genet ; 21(1): 110, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434471

RESUMO

BACKGROUND: Black women in the United States and Africa are at an increased risk for preeclampsia. Allelic variants in the gene for apolipoprotein LI, APOL1, are found only in populations of African ancestry, and have been shown to contribute significant risk for kidney disease. Recent studies suggest these APOL1 variants also may contribute risk for preeclampsia. METHODS: The association of preeclampsia with carriage of APOL1 risk alleles was evaluated in a case-control study of deliveries from black women at a single center in Cleveland, Ohio that included gross and histopathologic evaluations of placental tissues (395 cases and 282 controls). Using logistic regression models, associations between fetal APOL1 genotype and preeclampsia were evaluated using several case definitions based on prematurity and severity of preeclampsia, with uncomplicated term pregnancies as controls. Associations between APOL1 genotype and pathological features were also examined. RESULTS: The infant APOL1 genotype was significantly associated with preeclampsia in a dominant inheritance pattern with odds ratio of 1.41 (P=0.029, 95% CI 1.037, 1.926). Stratifying preeclampsia cases by preterm birth, significant associations were detected for both recessive (O.R.=1.70, P=0.038) and additive (O.R.=1.33, P=0.028) inheritance patterns. APOL1 genotype, however, was not significantly associated with pathological changes or other perinatal observations. CONCLUSIONS: Preeclampsia appears to be another disease associated with APOL1 variants, however, further studies are needed to increase confidence in the mode of inheritance. By understanding the association of APOL1 variants with preeclampsia, genetic screening tests for APOL1 may be useful to predict at-risk pregnancies and targeted interventions may be developed to improve pregnancy outcomes.

18.
J Surg Oncol ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32436293

RESUMO

BACKGROUND AND OBJECTIVES: Biologic therapy is changing the landscape of lung cancer treatment. The objectives of this study were to compare overall survival (OS) between patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant and adjuvant biologic therapy in combination with surgery and to evaluate the impact of chemotherapy on survival after combination biologic therapy and surgery. METHODS: The National Cancer Database was queried for cases of NSCLC from 2004 to 2016. Patient treatment was categorized into neoadjuvant and adjuvant biologic therapy in combination with surgery. Kaplan-Meier curves were generated to compare OS between treatment groups and between those who did and did not also undergo chemotherapy. Cox regression was used to identify factors predictive of OS. RESULTS: Six hundred seventy-three patients underwent both biologic therapy and surgery. The unadjusted overall 5-year OS was longer for patients undergoing neoadjuvant biologic therapy than for those undergoing adjuvant biologic therapy (P = .006), with OS being 56.2% and 33.0%, respectively. When comparing OS between those who did and did not undergo additional chemotherapy, no difference was observed. CONCLUSIONS: Neoadjuvant biologic therapy was associated with longer OS than adjuvant biologic therapy. Chemotherapy did not have an effect on OS when combined with biologic therapy and surgery.

19.
Curr Med Res Opin ; : 1-7, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32351136

RESUMO

Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women's Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA