Showing papers by "Lankenau Medical Center published in 2019"
Harvard University1, Yale Cancer Center2, Princess Margaret Cancer Centre3, Memorial Sloan Kettering Cancer Center4, Stanford University5, University of California, San Diego6, Lankenau Medical Center7, Johns Hopkins University8, Rush University Medical Center9, City of Hope National Medical Center10
TL;DR: There is a growing appreciation that EGFR-mutant NSCLCs can undergo SCLC transformation, and it is demonstrated that this occurs at an average of 17.8 months after diagnosis and cases are often characterized by Rb1, TP53, and PIK3CA mutations.
Abstract: PurposeApproximately 3% to 10% of EGFR (epidermal growth factor receptor) -mutant non–small cell lung cancers (NSCLCs) undergo transformation to small-cell lung cancer (SCLC), but their clinical co...
251 citations
TL;DR: Pembrolizumab after LAT for oligometastatic NSCLC appears to improve progression-free survival with no reduction in quality of life, and this study was powered for comparison with historical data on the first efficacy end point.
Abstract: Importance Patients with oligometastatic non–small cell lung cancer (NSCLC) may benefit from locally ablative therapy (LAT) such as surgery or stereotactic radiotherapy. Prior studies were conducted before the advent of immunotherapy, and a strong biological rationale for the use of immunotherapy exists in a minimal residual disease state. Objective To evaluate whether the addition of pembrolizumab after LAT improves outcomes for patients with oligometastatic NSCLC. Design, Setting, and Participants This single-arm phase 2 trial of pembrolizumab therapy was performed from February 1, 2015, through September 30, 2017, at an academic referral cancer center. The 51 eligible patients enrolled had oligometastatic NSCLC (≤4 metastatic sites) and had completed LAT to all known sites of disease. Data were analyzed from February 1, 2015, to August 23, 2018. Interventions Within 4 to 12 weeks of completing LAT, patients began intravenous pembrolizumab therapy, 200 mg every 21 days, for 8 cycles, with provision to continue to 16 cycles in the absence of progressive disease or untoward toxic effects. Main Outcomes and Measures The 2 primary efficacy end points were progression-free survival (PFS) from the start of LAT (PFS-L), which preceded enrollment in the trial, and PFS from the start of pembrolizumab therapy (PFS-P). The study was powered for comparison with historical data on the first efficacy end point. Secondary outcomes included overall survival, safety, and quality of life as measured by the Functional Assessment of Cancer Therapy–Lung instrument. Results Of 51 patients enrolled, 45 (24 men [53%]; median age, 64 years [range, 46-82 years]) received pembrolizumab. At the time of analysis, 24 patients had progressive disease or had died. Median PFS-L was 19.1 months (95% CI, 9.4-28.7 months), significantly greater than the historical median of 6.6 months (P = .005). Median PFS-P was 18.7 months (95% CI, 10.1-27.1 months). Eleven patients died. Overall mean (SE) survival rate at 12 months was 90.9% (4.3%); at 24 months, 77.5% (6.7%). Neither programmed death ligand 1 expression nor CD8 T-cell tumor infiltration was associated with PFS-L. Pembrolizumab after LAT yielded no new safety signals and no reduction in quality of life. Conclusions and Relevance Pembrolizumab after LAT for oligometastatic NSCLC appears to improve PFS with no reduction in quality of life. Trial Registration ClinicalTrials.gov identifier:NCT02316002
196 citations
University of British Columbia1, Baylor University2, Stanford University3, MedStar Washington Hospital Center4, Henry Ford Health System5, Cleveland Clinic6, Emory University7, Lankenau Medical Center8, Cornell University9, Pennsylvania State University10, Temple University11, North Central College12, NorthShore University HealthSystem13, Mayo Clinic14, Houston Methodist Hospital15, University of California, San Diego16
TL;DR: In this article, Suture-based pre-closure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortric aneurysm repair.
Abstract: Background: Open surgical closure and small-bore suture-based preclosure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic an
79 citations
Tel Aviv Sourasky Medical Center1, Sheba Medical Center2, Hospital Sant Joan de Déu Barcelona3, University of Bordeaux4, National Taiwan University5, Catholic University of Korea6, Beth Israel Deaconess Medical Center7, University of Amsterdam8, St George’s University Hospitals NHS Foundation Trust9, Paris Diderot University10, University of Turin11, Xiamen University12, Copenhagen University Hospital13, Tokyo Medical and Dental University14, Cardiovascular Institute of the South15, University of Girona16, Université libre de Bruxelles17, Hannover Medical School18, University of Padua19, Kansai Medical University20, Lankenau Medical Center21, University of Ulsan22
TL;DR: Current management after first arrhythmia episode is associated with high recurrence rate, and Alternative therapies, besides defibrillator implantation, should be considered.
45 citations
TL;DR: After introduction of this colon cancer quality measure, performance at CoC-accredited hospitals improved over the subsequent 13 years, and survival by hospital type paralleled measure compliance by hospitaltype.
Abstract: Many quality measures in cancer care are process measures. The rates of compliance for these measures over time have not been well described, and the relationships between measure compliance and survival are not well understood. The National Cancer Database, representing cancer registry data from approximately 1500 Commission on Cancer (CoC) cancer programs, was queried to determine the rates of compliance, with the CoC’s colon cancer quality measure requiring 12 regional lymph nodes be removed at resection. Data were assessed in 2003, before the measure was reported to programs, through 2015. Measure compliance and risk-adjusted survival were examined by hospital type. From 2003 to 2015, 544,018 cases of colon cancer were analyzed for number of nodes removed. In 2003, compliance was 52.8% and National Cancer Institute (NCI) centers had the highest compliance rate (69.0%), followed by academic cancer centers (61.9%), comprehensive community hospitals (50.9%), and community hospitals (44.0%). Between 2003 and 2015, compliance improved for all hospital types, although differences remained. Risk-adjusted survival in 2009 was better at NCI centers [hazard ratio (HR) 0.76] than at academic cancer centers (HR 0.90), which had better survivals than comprehensive community programs (HR 0.93) when compared with patients treated at community hospitals. After introduction of this quality measure, performance at CoC-accredited hospitals improved over the subsequent 13 years, and survival by hospital type paralleled measure compliance by hospital type. This demonstrated measurement may be associated with improvements in performance, and that there are differences in performance and outcome by hospital type.
29 citations
02 Oct 2019
TL;DR: In elderly individuals with cognitive disorders, a mechanism that involves disruption of nighttime sleep may underlie the association between β-amyloid deposition and cognitive impairment.
Abstract: Importance Evidence shows that sleep dysfunction and β-amyloid (Aβ) deposition work synergistically to impair brain function in individuals with normal cognition, increasing the risk of developing dementia later in life. However, whether Aβ continues to play an integral role in sleep dysfunction after the onset of cognitive decline in individuals with dementia is unclear. Objective To determine whether Aβ deposition in the brain is associated with subjective measures of sleep quality and cognition in elderly individuals with cognitive disorders. Design, Setting, and Participants A nested survey study was conducted at the Cognitive Disorders and Comprehensive Alzheimer Disease Center of Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Participants included patients aged 65 years and older with cognitive disorders verified by neuropsychological testing. Eligible participants were identified from a referral center–based sample of patients who underwent fluorine 18–labeled florbetaben positron emission tomography imaging at Thomas Jefferson University Hospital as part of the multicenter Imaging Dementia-Evidence for Amyloid Scanning study. Data collection and analysis occurred between November 2018 and March 2019. Main Outcomes and Measures Sleep quality was measured via responses to sleep questionnaires, Aβ deposition was measured via fluorine 18–labeled florbetaben positron emission tomography, and cognition was measured via Mini-Mental State Examination (MMSE) performance. Results Of the 67 eligible participants, 52 (77.6%) gave informed consent to participate in the study. Of the 52 enrolled participants (mean [SD] age, 76.6 [7.4] years), 27 (51.9%) were women. Daytime sleepiness was associated with Aβ deposition in the brainstem (B = 0.0063; 95% CI, 0.001 to 0.012;P = .02), but not MMSE performance (B = −0.01; 95% CI, −0.39 to 0.37;P = .96). The number of nocturnal awakenings was associated with Aβ deposition in the precuneus (B = 0.11; 95% CI, 0.06 to 0.17;P Conclusions and Relevance Nighttime sleep disruption may mediate the association between Aβ and cognitive impairment, suggesting that there is an underlying sleep-dependent mechanism that links Aβ burden in the brain to cognitive decline. Further elucidation of this mechanism may improve understanding of disease processes associated with Aβ accumulation.
25 citations
Harvard University1, Brown University2, Northwestern University3, University of Michigan4, Indiana University – Purdue University Indianapolis5, National Institutes of Health6, Ochsner Medical Center7, University of Washington8, Hunterdon Medical Center9, Lankenau Medical Center10, Mercy Medical Center (Baltimore, Maryland)11, Wake Forest University12, Albert Einstein College of Medicine13, Memorial Sloan Kettering Cancer Center14
TL;DR: Among women with DCIS who were WLE candidates based on conventional imaging, multiple factors were associated with conversion to mastectomy, and this study may provide useful preliminary information required for designing a planned randomized clinical trial.
Abstract: Importance Advanced diagnostics, such as magnetic resonance imaging (MRI) and gene expression profiles, are potentially useful to guide targeted treatment in patients with ductal carcinoma in situ (DCIS). Objectives To examine the proportion of patients who converted to mastectomy after MRI and the reasons for those conversions and to measure patient adherence to radiotherapy guided by the 12-gene DCIS score. Design, Setting, and Participants Analysis of a prospective, cohort, nonrandomized clinical trial that enrolled women with DCIS on core biopsy who were candidates for wide local excision (WLE) from 75 institutions from March 25, 2015, to April 27, 2016, through the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network trial E4112. Interventions Participants underwent breast MRI before surgery, and subsequent management incorporated MRI findings for choice of surgery. The DCIS score was used to guide radiotherapy recommendations among women with DCIS who had WLE as the final procedure and had tumor-free excision margins of 2 mm or greater. Main Outcomes and Measures The primary end point was to estimate the conversion rate to mastectomy and the reason for conversion. Results Of 339 evaluable women (mean [SD] age, 59.1 [10.1] years; 262 [77.3%] of European descent) eligible for WLE before MRI, 65 (19.2%; 95% CI, 15.3%-23.7%) converted to mastectomy. Of these 65 patients, conversion was based on MRI findings in 25 (38.5%), patient preference in 25 (38.5%), positive margins after attempted WLE in 10 (15.4%), positive genetic test results in 3 (4.6%), and contraindication to radiotherapy in 2 (3.1%). Among the 285 who had WLE performed after MRI as the first surgical procedure, 274 (96.1%) achieved successful breast conservation. Of 171 women eligible for radiotherapy guided by DCIS score (clear margins, absence of invasive disease, and score obtained), the score was low ( Conclusions and Relevance Among women with DCIS who were WLE candidates based on conventional imaging, multiple factors were associated with conversion to mastectomy. This study may provide useful preliminary information required for designing a planned randomized clinical trial to determine the effect of MRI and DCIS score on surgical management, radiotherapy, overall resource use, and clinical outcomes, with the ultimate goal of achieving greater therapeutic precision. Trial Registration ClinicalTrials.gov identifier:NCT02352883
22 citations
Sheba Medical Center1, University of Amsterdam2, University of Bordeaux3, Catholic University of Korea4, Tokyo Medical and Dental University5, National Taiwan University6, Beth Israel Deaconess Medical Center7, Tel Aviv Sourasky Medical Center8, Children's Medical Center of Dallas9, University of Turin10, Cardiovascular Institute of the South11, Xiamen University12, University of Padua13, Kansai Medical University14, St George’s University Hospitals NHS Foundation Trust15, University of Girona16, Université libre de Bruxelles17, University of Barcelona18, Copenhagen University Hospital19, Hannover Medical School20, Lankenau Medical Center21, University of Ulsan22, Tel Aviv University23
TL;DR: Asian patients with Brugada syndrome present almost exclusively as male adults, more often with aborted cardiac arrest and spontaneous type 1 BrS-ECG, however, they have less FHSCD and markedly lower SCN5A mutation rates.
19 citations
TL;DR: DIAGRAF-IKUR was the first study to show that using ICM to assess the effect of an AAD is feasible and the selective IKur inhibitor S66913 was safe but had no clinically meaningful effect at the time of early termination of the study.
Abstract: Aims Antiarrhythmic drugs (AADs) for the treatment of atrial fibrillation (AF) are associated with limited efficacy and adverse effects. Inhibition of the atrial current IKur, absent from the ventricle, is expected to be antiarrhythmic, without adverse cardiac effects, particularly ventricular pro-arrhythmic effects. Methods and results A randomized clinical trial in symptomatic paroxysmal AF patients being considered for ablation. The primary endpoint was AF burden (AFB) as measured by insertable continuous monitoring (ICM) devices. Screened patients had an ICM implanted and were included if AFB was between 1% and 70% after 4 weeks of recording. They were randomly allocated to 4-week treatment of a selective IKur inhibitor S66913 (5 mg, 25 mg, or 100 mg orally per day) or placebo. The study was to enroll 160 patients. The study was terminated prematurely, due to non-study related preclinical safety concerns, after 58 patients had been enrolled. The median AFB ranged from 4.3% to 10.3% at baseline in the four treatment groups. S66913 had no significant effect on AFB or on AFB plus atrial tachycardia (AT) burden, at any dosage; nor on any secondary endpoints including the number and duration of AT or AF episodes, and symptoms. The drug was well tolerated with no safety concern during the treatment or the extended clinical follow-up. Conclusions DIAGRAF-IKUR was the first study to show that using ICM to assess the effect of an AAD is feasible. The selective IKur inhibitor S66913 was safe but had no clinically meaningful effect at the time of early termination of the study.
16 citations
Medical College of Wisconsin1, Mayo Clinic2, Washington University in St. Louis3, Baptist Hospital of Miami4, Northwestern University5, University of Saskatchewan6, Thomas Jefferson University Hospital7, Cleveland Clinic8, University Hospitals of Cleveland9, Lankenau Medical Center10, Hamilton Health Sciences11, University of Oklahoma Health Sciences Center12, Wayne State University13, Vanderbilt University Medical Center14
TL;DR: In patients receiving HA-WBRT for brain metastases, extent of pretreatment WMI predicts posttreatment memory decline, suggesting a mechanism for radiation therapy–induced neurocognitive toxicity independent of hippocampal stem cell radiosensitivity.
Abstract: Purpose NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and Materials Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. Results In the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P Conclusions In patients receiving HA-WBRT for brain metastases, extent of pretreatment WMI predicts posttreatment memory decline, suggesting a mechanism for radiation therapy–induced neurocognitive toxicity independent of hippocampal stem cell radiosensitivity. Stability or improvement in HVLT after HA-WBRT for patients with higher pretreatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on neurocognition.
15 citations
University of Maryland, Baltimore1, Harvard University2, Novant Health3, Baptist Health4, Baptist Hospital of Miami5, Ochsner Health System6, Lankenau Medical Center7, University of Wisconsin-Madison8, University at Buffalo9, Veterans Health Administration10, University of Alabama at Birmingham11, Mayo Clinic12
TL;DR: This study reports periprocedural outcomes in a cohort of carotid artery stenting (CAS) performed for asymptomatic and symptomaticCarotid stenosis, the first national registry for CAS cosponsored by federal and industry partners.
TL;DR: The results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation.
Abstract: Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower 14 C-mannitol leakage across the cecal mucosa, consistent with a direct strengthening of colonic barrier function. Transcriptomic analyses of colitis tissues highlighted altered expression of genes involved in circadian rhythm, lipid metabolism, and inflammation, with a correction of the alterations by Bin1 mAb treatment to patterns characteristic of normal tissues. Overall, our results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation.
Sheba Medical Center1, French Institute of Health and Medical Research2, Catholic University of Korea3, Cardiovascular Institute of the South4, University of Turin5, Paris Diderot University6, National Taiwan University7, Tokyo Medical and Dental University8, Beth Israel Deaconess Medical Center9, Tel Aviv University10, Sunnybrook Health Sciences Centre11, Copenhagen University Hospital12, University of Copenhagen13, St George’s University Hospitals NHS Foundation Trust14, Xiamen University15, University of Amsterdam16, University of Girona17, Lankenau Medical Center18, Hannover Medical School19, University of Padua20, University of Pavia21, Kansai Medical University22, University of Ulsan23
TL;DR: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients and Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.
Abstract: Aims: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce. Methods and results: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics. Multivariate logistic regression models were utilized to identify which parameters predicted time to arrhythmia ≤5 years. The median time-to-first appropriate ICD therapy was 24.8 ± 2.8 months. A shorter time was observed in patients from Asian ethnicity (P < 0.05), those with syncope (P = 0.001), and those with Class IIa indication for ICD (P = 0.001). A longer time was associated with a positive family history of sudden cardiac death (P < 0.05). Multivariate Cox regression revealed shorter time-to-ICD therapy in patients with syncope [odds ratio (OR) 1.65, P = 0.001]. In 193 patients (76.6%), therapy was delivered during the first 5 years. Factors associated with this time were syncope (OR 0.36, P = 0.001), spontaneous Type 1 Brugada electrocardiogram (ECG) (OR 0.5, P < 0.05), and Class IIa indication (OR 0.38, P < 0.01) as opposed to Class IIb (OR 2.41, P < 0.01). A near-significant trend for female gender was also noted (OR 0.13, P = 0.052). Two score models for prediction of <5 years to shock were built. Conclusion: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients. Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.
15 May 2019
TL;DR: The value of physiologic dead space can see an increase in the value in lung disease states where the diffusion membrane of alveoli does not function properly or when there are ventilation/perfusion mismatch defects.
Abstract: Dead space represents the volume of ventilated air that does not participate in gas exchange. The two types of dead space are anatomical dead space and physiologic dead space. Anatomical dead space is represented by the volume of air that fills the conducting zone of respiration made up by the nose, trachea, and bronchi. This volume is considered to be 30% of normal tidal volume (500 mL); therefore, the value of anatomic dead space is 150 mL. Physiologic or total dead space is equal to anatomic plus alveolar dead space which is the volume of air in the respiratory zone that does not take part in gas exchange. The respiratory zone is comprised of respiratory bronchioles, alveolar duct, alveolar sac, and alveoli. In a healthy adult alveolar dead space can be considered negligible. Therefore, physiologic dead space is equivalent to anatomical. One can see an increase in the value of physiologic dead space in lung disease states where the diffusion membrane of alveoli does not function properly or when there are ventilation/perfusion mismatch defects.
TL;DR: As the clinician is faced with new acute renal failure, it is important to appreciate those factors that place patients at greater risk of anticoagulation-related nephropathy: conditions such as underlying chronic kidney disease patients and supratherapeutic international normalized ratio.
TL;DR: The incidence of intraoper PVL is low and postoperative renal failure was the only factor significantly associated with the development of a postoperative PVL in a contemporary consecutive cohort of patients following surgical aortic valve replacement.
Abstract: Objective: Our study investigates the incidence, cumulative incidence, natural history, and factors associated with intraoperative paravalvular leak (PVL) and the development of a postoperative PVL in a contemporary consecutive cohort of patients following surgical aortic valve replacement. Methods: A total of 636 patients underwent surgical aortic valve replacement from 2006 to 2016; 410 (64.5%) underwent minimally invasive aortic valve replacement and 226 (35.5%) underwent conventional aortic valve replacement. Primary outcomes were the incidence of intraoperative PVL and cumulative incidence of postoperative PVL. Secondary outcomes were the incidence of in-hospital and long-term death and need for reoperation. Results: The overall incidence of intraoperative PVL was 1.4% (95% confidence interval [CI]: 1% to 3%). All intraoperative PVLs developed in the hand-tied group. The overall incidence of postoperative PVL was 5.3% (95% CI: 4% to 7%). In the univariable and multivariable analyses, postoperative renal failure was the only factor significantly associated with the development of a postoperative PVL. Conclusions: The incidence of intraoperative PVL is low. Cumulative incidence of postoperative PVL was 3.1% (95% CI: 1.0% to 13.6%), 4.3% (95% CI: 1.3% to 16.5%), and 5.0% (95% CI: 1.4% to 17.9%) at 1, 3, and 5 years, respectively. All intraoperative PVLs occurred with hand-tied knots. A larger cohort may identify additional risk factors.
TL;DR: 10‐year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL.
Abstract: In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well-tolerated in previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma (iNHL). After a median patient follow-up of more than 108 months, we performed an intent-to-treat analysis of our 83 participants. Progression-free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten-year PFS rates for those with beta-2-microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10-year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long-term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10-year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL.
TL;DR: The empirical data show sleepwalking is characterized by a decrease in the inhibitory activity of GABAA - permitting or facilitating motor activity while alcohol has the opposite effect of increasing GAB AA and inhibiting motor activity, which is inconsistent with theories that alcohol is somehow a trigger or facilitator for sleepwalking.
TL;DR: Robust transcriptional differences between PARPi sensitive and resistant tumors accurately predict PARPi response in vitro and cisplatin response in vivo for multiple tumor types with or without known BRCA1/2 deficiency.
Abstract: PARP inhibitors (PARPi) are FDA approved for the treatment of BRCA1/2 deficient breast and ovarian cancer, but a growing body of pre-clinical evidence suggests the drug class holds therapeutic potential in other cancer types, independent of BRCA1/2 status. Large-scale pharmacogenomic datasets offer the opportunity to develop predictors of response to PARPi’s in many cancer types, expanding their potential clinical applicability. Response to the PARPi olaparib was used to identify a multi-gene PARPi response signature in a large in vitro dataset including multiple cancer types, such as breast, ovarian, pancreatic, lung cancer, osteosarcoma and Ewing sarcoma, using machine learning approaches. The signature was validated on multiple independent in vitro datasets, also testing for response to another PARPi, rucaparib, as well as two clinical datasets using the cisplatin response as a surrogate for PARPi response. Finally, integrative pharmacogenomic analysis was performed to identify drugs which may be effective in PARPi resistant tumors. A PARPi response signature was defined as the 50 most differentially transcribed genes between PARPi resistant and sensitive cell lines from several different cancer types. Cross validated predictors generated with LASSO logistic regression using the PARPi signature genes accurately predicted PARPi response in a training set of olaparib treated cell lines (80-89%), an independent olaparib treated in vitro dataset (66-77%), and an independent rucaparib treated in vitro dataset (80-87%). The PARPi signature also significantly predicted in vitro breast cancer response to olaparib in another separate experimental dataset. The signature also predicted clinical response to cisplatin and survival in human ovarian cancer and osteosarcoma datasets. Robust transcriptional differences between PARPi sensitive and resistant tumors accurately predict PARPi response in vitro and cisplatin response in vivo for multiple tumor types with or without known BRCA1/2 deficiency. These signatures may prove useful for predicting response in patients treated with PARP inhibitors.
14 Jun 2019
TL;DR: The results demonstrate that ROMA in AA women with adnexal masses have lower sensitivity for the detection of malignancy than does MIA, with the most marked results inAA women.
Abstract: Objective:To review and analyze the serum values of risk of ovarian malignancy algorithm (ROMA) and multivariate index assay (MIA) in subgroups of women who underwent surgery for adnexal masses to ...
01 Jan 2019
TL;DR: Interventions seeking to reduce numbers of NTM in the environment require further study, but avoidance of activities associated with a high risk of aerosolization of water, dusts, and soils can be recommended to individuals with host factors that deem them susceptible to NTM disease.
Abstract: Nontuberculous mycobacteria (NTM) are ubiquitous inhabitants of natural and man-made water sources as well as outdoor and indoor dusts and soils. Individuals that are susceptible to NTM pulmonary disease are likely acquiring infection through inhalation of aerosolized organisms and possibly also from aspiration of ingested organisms. Numerous studies have documented the colonization of municipal water supplies, commercial and institutional plumbing, and household plumbing with NTM. In addition, NTM have been found in high numbers in various natural and man-made dusts and soils. This chapter will review the current knowledge regarding environmental sources of NTM and the complex factors associated with their survival and transmissibility to humans. Interventions seeking to reduce numbers of NTM in the environment require further study, but avoidance of activities associated with a high risk of aerosolization of water, dusts, and soils can be recommended to individuals with host factors that deem them susceptible to NTM disease.
TL;DR: A 49-year-old woman presented after a respiratory infection with an abnormal chest roentgenogram demonstrating a cystic calcified mass at the base of the right lung and a very rare disorder was found.
TL;DR: A large number of patients with advanced malignant melanoma had a dismal prognosis with an estimated median overall survival of nine months, but therapy response rates and long-term survivability rates have improved since diagnosis.
Abstract: 9525Background: Historically, patients with advanced malignant melanoma had a dismal prognosis with an estimated median overall survival of nine months. Therapy response rates and long-term surviva...
TL;DR: A 67-year-old male with a history of rheumatic mitral stenosis and splenectomy presented with 1 week of fevers, chills and worsening dyspnea, and physical exam revealed no Chromobacter xylosoxidans.
TL;DR: JC is prevalent and, despite being 1 of its main goals, is not effective at teaching residents about biostatistics in its current form, so developing realistic, targeted curricula about biOSTatistics as adjuncts to current JC activities may help programs achieve these goals more readily.
01 May 2019
TL;DR: The case of a transgender female patient with retained foreign bodies in her neovagina, which required endoscopic therapy, is presented and the potential long-term complications that can arise from a nevagina after intestinal transfer are discussed.
Abstract: Intestinal vaginoplasty, first described in 1904, has more recently become a popular mechanism for gender-affirming surgery in the United States. We present the case of a transgender female patient with retained foreign bodies in her neovagina, which required endoscopic therapy, provide a brief review of the literature, and discuss the potential long-term complications that can arise from a neovagina after intestinal transfer. It is important that gastroenterologists have awareness and recognition of these issues, as surgical reconstruction using intestinal segments for transgender patients becomes more common.
TL;DR: Percutaneous retrograde cardioplegia combined with antegrade cardiolysis and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement.
Abstract: OBJECTIVES Patients with patent internal thoracic artery (ITA) grafts after prior coronary artery bypass grafting surgery who require aortic valve replacement (AVR) pose unique technical challenges for safe and optimal myocardial protection. The purpose of this study is to review our short- and long-term outcomes with redo minimally invasive AVR in patients with patent in situ ITA grafts. METHODS From 2008 to 2016, 48 patients with at least 1 patent in situ mammary artery graft underwent minimally invasive AVR. Preoperative computed tomography was performed in all patients to evaluate the relationship of patent grafts to the sternum. Retrograde coronary sinus and pulmonary vent catheters were placed via the right internal jugular vein. The in situ ITA grafts were not clamped during AVR. Transverse aortotomy, taking care to avoid the grafts arising from the aorta, was performed to expose the aortic valve. RESULTS The median age of the patients was 78 years [Quartile 1 (Q1)-Quartile 3 (Q3): 71-81]. Thirty-nine (81%) patients were men, and 46 (96%) patients had aortic stenosis. The median cardiopulmonary bypass and cross-clamp times were 124 (Q1-Q3: 108-164) and 92 (Q1-Q3: 83-116) min, respectively. Moderate hypothermia at 28-30°C was used in all patients. Most patients received cold blood cardioplegia with antegrade induction and continuous retrograde delivery. Four patients received only retrograde delivery due to some degree of aortic insufficiency. Thirty-day mortality was 4% (2 of 48 patients). There was no conversion to full sternotomy, and no reoperations were performed for postoperative bleeding or sternal wound infection. Excluding the 2 patients who died in the hospital, the median postoperative length of stay was 7 days (Q1-Q3: 5-8). Overall survival at 1, 5 and 10 years was 94%, 87% and 44%, respectively. CONCLUSIONS Percutaneous retrograde cardioplegia combined with antegrade cardioplegia and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement. This strategy combined with a minimally invasive approach may reduce surgical trauma, and is a safe and effective technique in these challenging patients.
01 Jan 2019
TL;DR: There has always been a necessary balance in medicine between the principles of diagnosis and treatment, but the resources required to achieve such a balance are constantly changing and the ever-expanding diversity and variable potency of medications available to practitioners are made increasingly difficult.
Abstract: There has always been a necessary balance in medicine between the principles of diagnosis and treatment. However, the resources required to achieve such a balance are constantly changing. While the applied elements of medical diagnostics continue to evolve scientifically, the selection and delivery of a particular treatment regimen still require a human touch. Accordingly, at its most fundamental level, the successful delivery of a specific therapeutic intervention and the prevention of error require administration of the correct medication in the correct dose via the correct route at the correct time to the correct patient. These fundamental steps are made increasingly difficult by the ever-expanding diversity and variable potency of medications available to practitioners.