Publications by authors named "Shouhao Zhou"

81 Publications

SNP and Haplotype Interaction Models Reveal Association of Surfactant Protein Gene Polymorphisms With Hypersensitivity Pneumonitis of Mexican Population.

Front Med (Lausanne) 2020 5;7:588404. Epub 2021 Jan 5.

Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, United States.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of common environmental organic particles. Surfactant proteins (SPs) play a role in innate immunity and surfactant function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes of the SP genes associate with HP. Seventy-five HP patients caused by avian antigen and 258 controls, asymptomatic antigen exposed and non-exposed were enrolled. SNP association was performed using logistic regression analysis and SNP-SNP interaction models. Based on odds ratio, regression analyses showed association of (a) rs7316_G, 1A (protective) compared to antigen exposed; (b) male sex, smoking, rs721917_T and rs1130866_T (protective) compared to non-exposed controls with HP; (c) compared to antigen exposed, 25 interactions associated with HP in a three-SNP model; (d) compared to non-exposed, (i) rs1136451 associated with increased, whereas rs1136450 and rs1130866 associated with lower HP risk, (ii) 97 interactions associated with HP in a three-SNP model. The majority of SNP-SNP interactions associated with increased HP risk involved SNPs of the hydrophilic SPs, whereas, the majority of interactions associated with lower HP risk involved SNPs of both hydrophilic and hydrophobic SPs; (e) haplotypes of SP genes associated with HP risk. The complexity of SNPs interactions of the genes observed indicate that the lung inflammatory response to avian antigens is modulated by a complex gene interplay rather than by single SNPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.588404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813780PMC
January 2021

Trends and patterns in the use of opioids among metastatic breast cancer patients.

Sci Rep 2020 12 10;10(1):21698. Epub 2020 Dec 10.

Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.

Opioid use among metastatic breast cancer (MBC) patients has not been well-studied. This study examined the trends and patterns of opioid use among working-age, privately insured patients diagnosed with MBC. Using MarketScan data, we identified female patients diagnosed with MBC in 2006-2015. We determined the proportion of patients who filled a prescription for an opioid and calculated days' supply and daily morphine milligram equivalents (MMEs) from 1 year prior to diagnosis till 1 year after. We assessed the trend in opioid use over the 10-year study period and examined opioid usage patterns after the diagnosis of MBC. Among 24,752 patients included, 11,579 (46.8%) had an opioid prescription within 1 year before diagnosis of MBC, and 20,416 (81.4%) had an opioid prescription within 1 year after diagnosis. The proportion of patients with opioid prescriptions after diagnosis was relatively stable from 2006 to 2015. However, both the median daily MME and median days' supply decreased over time with most of the decline from the subgroup of patients with prior prescription opioid use. Most patients received an opioid prescription in the first month after diagnosis (57.3%), dropping to approximately 20% from 3 to 12 months after diagnosis. Also, the median days' supply increased substantially during the year after diagnosis for patients who received opioids (from 7 to 19). Most women with MBC require opioid analgesia within the first month after diagnosis. Judicious, long-term management of pain after diagnosis of MBC will continue to be necessary for many patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-78569-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729956PMC
December 2020

Hypomagnesemia and incidence of osteoradionecrosis in patients with head and neck cancers.

Head Neck 2021 Feb 23;43(2):613-621. Epub 2020 Oct 23.

Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Background: We aimed to determine whether hypomagnesemia predicts osteoradionecrosis development in patients with squamous cell carcinoma of the oropharynx and oral cavity who received platinum-based concurrent chemoradiation with or without induction therapy.

Methods: We reviewed data from patients with head and neck cancers who had undergone chemoradiation with weekly cisplatin/carboplatin between January 1, 2010 and December 31, 2014 at our institution. Pathologic features, laboratory test results, disease stage, and social histories were recorded. The association between hypomagnesemia and osteoradionecrosis was analyzed controlling for known confounding factors.

Results: Hypomagnesemia during cancer treatment was associated with osteoradionecrosis development (HR = 2.72, P = .037) independent of total radiation dose (HR = 1.07, P = .260) and smoking history (HR = 2.05, P = .056) among the patients who received platinum-based induction chemotherapy followed by concurrent chemoradiation.

Conclusions: Hypomagnesemia was predictive of the development of osteoradionecrosis in patients with cancers of the oropharynx and oral cavity receiving platinum-based induction followed by concurrent chemoradiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26510DOI Listing
February 2021

Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia: A Systematic Review and Meta-analysis.

JAMA Oncol 2020 Oct 8. Epub 2020 Oct 8.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston.

Importance: Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.

Objective: To examine the association between MRD status and disease-free survival (DFS) and overall survival (OS) in patients with AML using scientific literature.

Data Sources: Clinical studies on AML published between January 1, 2000, and October 1, 2018, were identified via searches of PubMed, Embase, and MEDLINE.

Study Selection: Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies that assessed DFS or OS by MRD status in patients with AML were included. Reviews, non-English-language articles, and studies reporting only outcomes after hematopoietic cell transplantation or those with insufficient description of MRD information were excluded.

Data Extraction And Synthesis: Study sample size, median patient age, median follow-up time, MRD detection method, MRD assessment time points, AML subtype, specimen source, and survival outcomes were extracted. Meta-analyses were performed separately for DFS and OS using bayesian hierarchical modeling.

Main Outcomes And Measures: Meta-analyses of survival probabilities and hazard ratios (HRs) were conducted for OS and DFS according to MRD status.

Results: Eighty-one publications reporting on 11 151 patients were included. The average HR for achieving MRD negativity was 0.36 (95% bayesian credible interval [CrI], 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The estimated 5-year DFS was 64% for patients without MRD and 25% for those with MRD, and the estimated OS was 68% for patients without MRD and 34% for those with MRD. The association of MRD negativity with DFS and OS was significant for all subgroups, with the exception of MRD assessed by cytogenetics or fluorescent in situ hybridization.

Conclusions And Relevance: The findings of this meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML. The value of MRD negativity appears to be consistent across age groups, AML subtypes, time of MRD assessment, specimen source, and MRD detection methods. These results support MRD status as an end point that may allow for accelerated evaluation of novel therapies in AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2020.4600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545346PMC
October 2020

Comparison of virtual to true unenhanced abdominal computed tomography images acquired using rapid kV-switching dual energy imaging.

PLoS One 2020 23;15(9):e0238582. Epub 2020 Sep 23.

Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Objective: To compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages.

Methods: VUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling.

Results: Quantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney.

Conclusions: Significant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238582PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511018PMC
October 2020

Evaluating the Utility of Toxicologic Analysis in Pediatric Out-of-Hospital Cardiac Arrest.

J Emerg Med 2020 Nov 8;59(5):e167-e174. Epub 2020 Sep 8.

Pediatric Critical Care Medicine, Department of Pediatrics, Penn State Hershey Children's Hospital, Hershey, Pennsylvania.

Background: The cause of a pediatric out-of-hospital cardiac arrest (OHCA) may go unexplained in the emergency department setting but can be secondary to a toxicologic etiology. It is unclear how toxicologic screens are used in the postarrest period after a pediatric OHCA.

Objectives: The primary objectives are to describe 1) when the toxicology screen (urine and serum) is used, 2) patient characteristics, and 3) toxicology screen results. We hypothesized that toxicology screens are frequently used but that positive results are uncommon.

Methods: This was a retrospective study of pediatric OHCA patients admitted to the Penn State Health Children's Hospital pediatric intensive care unit as transfers from the emergency department between January 1, 2011 and May 31, 2018. We reviewed the electronic health record and evaluated for toxicology screen completion, patient characteristics, and toxicology screen results.

Results: One hundred forty-one patients had a pediatric OHCA. Sixty-three (44.7%) patients did not have a toxicology screen completed. A toxicology screen had a higher completion rate for children >11 years of age (n = 26 [78.8%]; p = 0.0024), and in unwitnessed arrests (n = 48 [66.7%]; p = 0.0052). Four cases (5.1%) revealed the presence of substances that were not administered by a medical provider or were illicit.

Conclusion: Our study found that in pediatric OHCA, toxicologic screens were completed but were not routinely sent in our institution. There may be factors such as clinician bias or the severity of a patient's illness that impact the approach to toxicologic screening in pediatric OHCA. In addition to the history and physical examination, emergency physician and pediatric intensivists should consider routinely sending toxicologic screens to assist in uncovering any accidental or malicious explanation for the event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jemermed.2020.07.020DOI Listing
November 2020

Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis.

Blood Adv 2020 07;4(13):2927-2938

Department of Lymphoma and Myeloma and.

Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (>5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2019001350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362354PMC
July 2020

Celestial Versus Terrestrial Travel-An Analysis of Spaceflight Fatalities and Comparison to Other Modes of Transportation.

Am J Med 2020 11 25;133(11):1274-1279. Epub 2020 Jun 25.

Department of Public Health Sciences, Division of Biostatistics and Bioinformatics, Penn State Cancer Institute, Penn State University, Hershey.

With the advent of commercial human spaceflight, it is important to analyze the historical safety of humans traveling to, in, and from space. We break down the fatality rates of human spaceflight and compare them to those of several terrestrial transportation modes. We created a database of human space travel, containing the vehicles, launches, and the total time and distance traveled. For the 4 fatal space missions and 18 fatalities, we determined the fatality rates, calculated by several methods, including rates per trip, person, and distance traveled, stratified by the mission segment affected. Two of the 326 launches did not reach space, and 8 others were suborbital. There have been 1285 person-launches to space; the total time in space is estimated to be 55,939 person-days; and the total distance traveled is approximately 23.5 billion person-miles. One fatal trip occurred on the way to orbit and the other 3 during the return. There has yet to be a fatality in orbit, and there have been none on any space flight since 2003. The per-trip and per-person fatality rates are 1.2% and 1.4%, respectively, but the per mile rate is much lower, depending on the flight segment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2020.05.023DOI Listing
November 2020

Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients.

Int J Cancer 2020 Dec 23;147(12):3550-3559. Epub 2020 Jun 23.

Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Neuroblastoma (NB) is a deadly childhood disease that carries a 50% chance of relapse for anyone in remission and similar level of 5-year survival. We investigated the value of our proprietary approach-cell surface vimentin (CSV) positive circulating tumor cells (CTC) to monitor treatment response and predict relapse in NB patients under remission in a Phase II long-term preventative clinical trial. We longitudinally analyzed peripheral blood samples from 93 patients for 27 cycles (~25 months) and discovered that the presence of CSV CTCs in the first two sequential samples (baseline, cycle 4 [month 3-4]) was a significant indicator of earlier relapse. We observed strong correlation between relapse-free survival (RFS) and lack of CSV CTCs in first 4 cycles of therapy (95%). There was sensitivity reaching 100% in predicting RFS in patients who had neither CSV CTCs nor MycN amplification. Of note, the low number of CSV CTCs seems equivalent to low tumor load because the prevention therapy difluoromethylornithine yields faster reduction of relapse risk when none or only 1-2 CSV CTCs (every 6 mL) are present in the blood samples compared to >3 CSV CTCs. To the best of our knowledge, this is the first study that directly observes CTCs in under remission NB patients for relapse prediction and the first to gather sequential CSV CTC data in any study in a long-term longitudinal manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839076PMC
December 2020

Prolonged Opioid Use After Surgery for Early-Stage Breast Cancer.

Oncologist 2020 10 2;25(10):e1574-e1582. Epub 2020 Jun 2.

Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Introduction: This study examined the patterns of prolonged opioid use and the factors associated with higher risk of prolonged opioid use among opioid-naïve working-age patients with early-stage breast cancer.

Methods: Using MarketScan data, the study identified 23,440 opioid-naïve patients who received surgery for breast cancer between January 2000 and December 2014 and filled at least one opioid prescription attributable to surgery. Prolonged opioid use was defined as one or more prescriptions for opioids within 90 to 180 days after surgery and defined extra-prolonged opioid use as one or more opioid prescriptions between 181 and 365 days after surgery. Multivariable logistic regressions were performed to ascertain factors associated with prolonged and extra-prolonged use of opioids.

Findings: Of the 23,440 patients, 4,233 (18%) had prolonged opioid use, and 2,052 (9%) had extra-prolonged opioid use. Patients who received mastectomy plus reconstruction had the highest rate of prolonged opioid use (38%) followed by mastectomy alone (15%). A multivariable logistic regression confirmed that patients with mastectomy and reconstruction had the highest odds ratio of prolonged opioid use compared to lumpectomy and whole breast irradiation (adjusted odds ratio, 5.6; 95% confidence interval, 5.1-6.1). Mean daily opioid dose was consistently high without any obvious dosage reduction among patients with opioid use.

Interpretation: This large observational study showed a high rate of prolonged opioid use among patients who received surgery for early-stage breast cancer and found significant difference in prolonged opioid use by treatment type.

Implications For Practice: This large observational study found a high rate of prolonged opioid use among working-age patients with early-stage breast cancer who received curative surgery, especially among patients who received mastectomy. Among patients with opioid use, the mean daily opioid dose was consistently high without any obvious dosage tapering. This study highlights the need to emphasize appropriate opioid therapy and potential dosage reduction or discontinuation among patients with early-stage breast cancer who received surgical interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543235PMC
October 2020

Clinical characteristics, management, and outcome of incidental pulmonary embolism in cancer patients.

Blood Adv 2020 04;4(8):1606-1614

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Incidental pulmonary embolisms (IPEs) are common in cancer patients. Examining the characteristics and outcomes of IPEs in cancer patients can help to ensure proper management, promoting better outcomes. To determine the clinical characteristics, management, and outcomes of IPEs for cancer patients, we conducted a 1:2 ratio case-control study and identified all consecutive patients with IPE who visited the emergency department at The University of Texas MD Anderson Cancer Center between 1 January 2006 and 1 January 2016. Each IPE case was matched with 2 controls using a propensity score obtained using logistic regression for IPE status with other factors affecting overall survival. A total of 904 confirmed cases were included in the analysis. IPE frequently occurred during the first year after cancer diagnosis (odds ratio [OR], 2.79; 95% confidence interval [95% CI], 2.37-3.29; P < .001). Patients receiving cytotoxic chemotherapy had a nearly threefold greater risk of developing IPE (OR, 2.87; 95% CI, 2.42-3.40; P < .001). In-hospital mortality was 1.9%. The 7- and 30-day mortality rates among the cases were 1.8% and 9.9%, respectively, which was significantly higher than in the control groups: 0.2% and 3.1%, respectively (P < .001). IPE was associated with reduced overall survival (hazard ratio [HR], 1.93; 95% CI, 1.74-2.14; P < .001). Concurrent incidental venous thromboembolism was identified in 189 of the patients (20.9%) and was also associated with reduced overall survival (HR, 1.65; 95% CI, 1.21-2.25; P = .001). Our results show that IPE events are associated with poor outcomes in cancer patients. Proper management plans similar to those of symptomatic pulmonary embolisms are essential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020001501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189276PMC
April 2020

Long-term causes of death among pediatric patients with cancer.

Cancer 2020 Jul 16;126(13):3102-3113. Epub 2020 Apr 16.

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania.

Background: The objectives of this study were to characterize the risk of death (1) from the primary cancer vs competing cause of death; and (2) from various causes of death vs the general poplation. The relative risk of death after a pediatric cancer diagnosis versus the general population and the risk of death from a primary cancer diagnosis versus competing causes of death.

Methods: This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database (1980-2015) and included patients aged 0 to 19 years at the time of diagnosis. Observed deaths were calculated; the risk of death versus the general population was assessed with standardized mortality ratios (SMRs). Competing risk models for the cause of death were performed.

Results: There were 58,356 patients who were diagnosed, and the mortality rate was 22.8%. To assess causes of death, 6996 patients who died during the study period were included (45,580 total person-years at risk): 5128 (73%) died of their primary cancer, and 1868 (27%) died of a competing cause. Among all patients, the rate of death from the index cancer was higher than the rate of death from another cause within the first 5 years after diagnosis. The risk of death from a nonprimary cancer began to supersede the rate of death from the primary cancer 10 years after diagnosis for patients with germ cell tumors, lymphomas, and sarcomas. SMRs for the primary cancer were highest within the first 5 years after diagnosis for all cancers (SMRs, 100-50,000; P < .0001). The risk of death from competing causes (heart disease, suicide, and sepsis) was elevated (SMR, >100; P < .001). The risk of dying of heart disease was high, especially for patients with astrocytomas (SMR, 47.84; 95% confidence interval [CI], 27.87-76.59) and neuroblastomas (SMR, 98.59; 95% CI, 47.28-181.32). The risk of dying of suicide was high in most patients, particularly for those with osteosarcomas (SMR, 111.40; 95% CI, 2.82-620.69), Hodgkin lymphomas (SMR, 62.35; 95% CI, 34.89-102.83), and gonadal germ cell tumors (SMR, 28.97; 95% CI, 12.51-57.09).

Conclusions: The cause of death for patients with gonadal germ cell tumors, lymphomas, and sarcomas is more commonly a secondary cancer or noncancerous cause than the primary disease; their risk of death from competing causes (heart disease, suicide, and sepsis) rises throughout life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32885DOI Listing
July 2020

Factors Associated With Hospital Decisions to Purchase Robotic Surgical Systems.

MDM Policy Pract 2020 Jan-Jun;5(1):2381468320904364. Epub 2020 Feb 2.

Department of Surgery, Division of Outcomes Research and Quality, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvani.

Robotic surgical systems are expensive to own and operate, and the purchase of such technology is an important decision for hospital administrators. Most prior literature focuses on the comparison of clinical outcomes between robotic surgery and other laparoscopic or open surgery. There is a knowledge gap about what drives hospitals' decisions to purchase robotic systems. To identify factors associated with a hospital's acquisition of advanced surgical systems. We used 2002 to 2011 data from the State of California Office of Statewide Health Planning and Development to examine robotic surgical system purchase decisions of 476 hospitals. We used a probit estimation allowing heteroscedasticity in the error term including a set of two equations: one binary response equation and one heteroscedasticity equation. During the study timeframe, there were 78 robotic surgical systems purchased by hospitals in the sample. Controlling for hospital characteristics such as number of available beds, teaching status, nonprofit status, and patient mix, the probit estimation showed that market-level directly relevant surgery volume in the previous year (excluding the hospital's own volume) had the largest impact. More specifically, hospitals in high volume (>50,000 surgeries v. 0) markets were 12 percentage points more likely to purchase robotic systems. We also found that hospitals in less competitive markets (i.e., Herfindahl index above 2500) were 2 percentage points more likely to purchase robotic systems. This study has limitations common to observational database studies. Certain characteristics such as cultural factors cannot be accurately quantified. Our findings imply that potential market demand is a strong driver for hospital purchase of robotic surgical systems. Market competition does not significantly increase the adoption of new expensive surgical technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2381468320904364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997967PMC
February 2020

Renal Replacement Therapy in Patients With Stage IV Cancer Admitted to the Intensive Care Unit With Acute Kidney Injury at a Comprehensive Cancer Center Was Not Associated With Survival.

Am J Hosp Palliat Care 2020 Sep 27;37(9):707-715. Epub 2020 Jan 27.

Sections of Nephrology and Supportive Care, West Virginia University School of Medicine, Morgantown, WV, USA.

Introduction: In patients with advanced cancer, prolongation of life with treatment often incurs substantial emotional and financial expense. Among hospitalized patients with cancer since acute kidney injury (AKI) is known to be associated with much higher odds for hospital mortality, we investigated whether renal replacement therapy (RRT) use in the intensive care unit (ICU) was a significant independent predictor of worse outcomes.

Methods: We retrospectively reviewed patients admitted in 2005 to 2014 who were diagnosed with stage IV solid tumors, had AKI, and a nephrology consult. The main outcomes were survival times from the landmark time points, inpatient mortality, and longer term survival after hospital discharge. Logistic regression and Cox proportional regression were used to compare inpatient mortality and longer term survival between RRT and non-RRT groups. Propensity score-matched landmark survival analyses were performed with 2 landmark time points chosen at day 2 and at day 7 from ICU admission.

Results: Of the 465 patients with stage IV cancer admitted to the ICU with AKI, 176 needed RRT. In the multivariate logistic regression model after adjusting for baseline serum albumin and baseline maximum Sequential Organ Failure Assessment (SOFA), the patients who received RRT were not significantly different from non-RRT patients in inpatient mortality (odds ratio: 1.004 [95% confidence interval: 0.598-1.684], = .9892). In total, 189 patients were evaluated for the impact of RRT on long-term survival and concluded that RRT was not significantly associated with long-term survival after discharge for patients who discharged alive. Landmark analyses at day 2 and day 7 confirmed the same findings.

Conclusions: Our study found that receiving RRT in the ICU was not significantly associated with inpatient mortality, survival times from the landmark time points, and long-term survival after discharge for patients with stage IV cancer with AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1049909120902115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363512PMC
September 2020

The association between weight stability and parenteral nutrition characteristics and survival in patients with colorectal cancer.

Gastroenterol Rep (Oxf) 2019 Dec 17;7(6):419-425. Epub 2019 Jun 17.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objective: Knowledge about the impact of metabolic disturbances and parenteral nutrition (PN) characteristics on the survival of cancer patients receiving PN is limited. We aimed to assess the association between clinical and PN characteristics and survival in colorectal-cancer patients receiving PN support.

Methods: Our study included 572 consecutive colorectal-cancer patients who had received PN support between 2008 and 2013. Patient characteristics, body mass index, weight, medical/surgical history, indication for PN, PN data and survival were recorded. Associations between clinical and PN characteristics and survival were analysed with important confounding factors.

Results: The final cohort included 437 evaluable patients, with a mean age of 57 years. Eighty-one percent of the study population had advanced stage of colorectal cancer. Unstable weight (weight change ≥2.5%) prior to PN initiation [hazard ratio (HR) = 1.41,  = 0.023] was adversely associated with survival after adjusting for multiple factors including cancer stage. Bowel obstruction (HR = 1.75,  = 0.017) as a PN indication was associated with worse survival when compared with without bowel obstruction. Higher PN amino acid by ideal body weight (g•kg) (HR = 0.59,  = 0.029) was associated with longer survival, whereas a higher percentage of non-PN intravenous calories (HR = 1.04,  = 0.011) was associated with shorter survival independently of confounding factors.

Conclusions: Body mass index and weight stability can be useful nutritional indices for survival prediction in cancer patients receiving PN. PN planning should take into account of non-PN calories to achieve optimal energy support and balance. Future research is needed to define optimal PN amino-acid requirement and energy balance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gastro/goz021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911996PMC
December 2019

A population-based study of cardiovascular disease mortality risk in US cancer patients.

Eur Heart J 2019 12;40(48):3889-3897

Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.

Aims: This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis.

Methods And Results: The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973-2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at <35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89-3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population.

Conclusion: The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehz766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925383PMC
December 2019

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages.

Neuro Oncol 2020 04;22(4):539-549

Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.

Methods: In an open-label, single-center, single-arm phase II "window-of-opportunity" trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.

Results: No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients' recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.

Conclusions: Immune analyses indicated that pembrolizumab anti-programmed cell death 1 (PD-1) monotherapy alone can't induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noz185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158647PMC
April 2020

Pain and Dysfunction with Sexual Activity after Inguinal Hernia Repair: Systematic Review and Meta-Analysis.

J Am Coll Surg 2020 02 14;230(2):237-250.e7. Epub 2019 Nov 14.

Department of Surgery, Penn State Hershey College of Medicine and Milton S. Hershey Medical Center, Hershey, PA. Electronic address:

Background: The reported incidence rates of sexual dysfunction (SD) and pain with sexual activity (PSA) after inguinal hernia repair in males vary considerably. This meta-analysis explores the rates of SD and PSA after different surgical and anesthesia types to understand patient risk after inguinal hernia repair.

Study Design: We performed a systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to search 3 databases (EMBASE, MEDLINE, and Cochrane Library). We identified retrospective, prospective, and randomized controlled trial studies, published on or before March 1, 2019, reporting on SD and PSA after inguinal hernia repair. We used random-effects models to calculate pooled estimates of incidence rates of SD and PSA after inguinal hernia repair. Subgroup meta-analyses and meta-regression were used to explore sources of variation.

Results: A total of 4,884 patients from 12 studies were identified. Study-level median age at the time of repair was 52.3 years old, and study-level median follow-up was 10.5 months. Definitions of SD and PSA focused on completion of intercourse for the former and pain with erection/ejaculation for the latter. The overall incidence of new-onset, postoperative SD was 5.3% (95% CI 3.6% to 7.9%) and of PSA was 9.0% (95% CI 5.8% to 13.6%). Rates of SD associated with minimally invasive surgical (MIS) and open repair were, respectively, 7.8% (95% CI 5.4% to 11.3%) and 3.7% (95% CI 2.0% to 6.8%); rates of PSA were 7.4% (95% CI 4.7% to 11.5%) and 12.5% (95% CI 6.4% to 23.3%), respectively.

Conclusions: Sexual dysfunction and PSA are not rare after inguinal hernia repair. They should be included in preoperative discussions and as standard metrics in reporting outcomes of repair in large cohorts or trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamcollsurg.2019.10.010DOI Listing
February 2020

Racial Differences in the Incidence and Survival of Patients With Neuroendocrine Tumors.

Pancreas 2019 Nov/Dec;48(10):1373-1379

Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Objectives: The incidence of neuroendocrine tumors (NETs) has been steadily increasing. Racial differences in the incidence and survival are mostly unknown. This study examines the racial differences and the underlying causes.

Methods: We conducted a retrospective, population-based study using datasets from Surveillance, Epidemiology, and End Results (SEER) cancer registry and SEER data linked with Medicare claims (SEER-Medicare). We examined the incidence rates and the effects of patient demographics, clinical characteristics, and socioeconomic factors on survival.

Results: Of the 15,786 and 1731 cases from SEER and SEER-Medicare, 1991 and 163 were blacks, respectively. We found that blacks had higher NET incidence for all stages, with the largest difference noted in the local stage (4.3 vs 2.6 per 100,000 in whites). We found worse survival for distant-stage black patients, although they more often had clinical factors typically associated with better prognosis in NETs. However, they were also found to have significant unfavorable differences in socioeconomic and sociodemographic factors.

Conclusions: Blacks have higher incidence of NETs and worse survival compared with other races, especially whites. The influences of neighborhood socioeconomic, sociodemographic, and marital status suggest that social determinants, support mechanisms, and access to health care may be contributing factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001431DOI Listing
September 2020

Technical Note: Proof of concept for radiomics-based quality assurance for computed tomography.

J Appl Clin Med Phys 2019 Nov 14;20(11):199-205. Epub 2019 Oct 14.

MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.

Purpose: Routine quality assurance (QA) testing to identify malfunctions in medical imaging devices is a standard practice and plays an important role in meeting quality standards. However, current daily computed tomography (CT) QA techniques have proven to be inadequate for the detection of subtle artifacts on scans. Therefore, we investigated the ability of a radiomics phantom to detect subtle artifacts not detected in conventional daily QA.

Methods: An updated credence cartridge radiomics phantom was used in this study, with a focus on two of the cartridges (rubber and cork) in the phantom. The phantom was scanned using a Siemens Definition Flash CT scanner, which was reported to produce a subtle line pattern artifact. Images were then imported into the IBEX software program, and 49 features were extracted from the two cartridges using four different preprocessing techniques. Each feature was then compared with features for the same scanner several months previously and with features from controlled CT scans obtained using 100 scanners.

Results: Of 196 total features for the test scanner, 79 (40%) from the rubber cartridge and 70 (36%) from the cork cartridge were three or more standard deviations away from the mean of the controlled scan population data. Feature values for the artifact-producing scanner were closer to the population mean when features were preprocessed with Butterworth smoothing. The feature most sensitive to the artifact was co-occurrence matrix maximum probability. The deviation from the mean for this feature was more than seven times greater when the scanner was malfunctioning (7.56 versus 1.01).

Conclusions: Radiomics features extracted from a texture phantom were able to identify an artifact-producing scanner as an outlier among 100 CT scanners. This preliminary analysis demonstrated the potential of radiomics in CT QA to identify subtle artifacts not detected using the currently employed daily QA techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acm2.12750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839380PMC
November 2019

Dose-dependent effect of aerobic exercise on inflammatory biomarkers in a randomized controlled trial of women at high risk of breast cancer.

Cancer 2020 01 30;126(2):329-336. Epub 2019 Sep 30.

Department of Public Health Sciences, Pennsylvania State University, Hershey, Pennsylvania.

Background: Increased levels of inflammation are associated with many diseases, including cancer. Physical activity can lower breast cancer risk as well as levels of inflammation. The Women In Steady Exercise Research (WISER) Sister trial was a randomized controlled trial that investigated the effects of a dosed, moderate to vigorous, aerobic exercise intervention on levels of inflammation in premenopausal women who were at high risk of developing breast cancer.

Methods: Participants were randomized to control (<75 minutes per week; 41 patients), low-dose exercise (150 minutes per week; 38 patients), or high-dose exercise (300 minutes per week; 37 patients) groups. The 5-menstrual cycles-long, home-based treadmill exercise intervention gradually increased in minutes per week and intensity up to a maximum of 80% of the age-predicted maximum heart rate. Blood was collected at baseline and at follow-up and assayed for chemokine (C-C motif) ligand 2 (CCL2), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α).

Results: A linear dose-response relationship was observed for the proinflammatory biomarkers CCL2 (%Δ of -5.44% in the control group, -0.03% in the low-dose exercise group, and 1.54% in the high-dose exercise group), IL-12 (%Δ of -21.5% in the control group, 38.2% in the low-dose exercise group, and 25.8% in the high-dose exercise group,) and TNF-α (%Δ of -4.69% in the control group, 9.51% in the low-dose exercise group, and 15.7% in the high-dose exercise group) but not for the anti-inflammatory biomarker IL-10 (%Δ of 5.05% in the control group, 6.05% in the low-dose exercise group, and 10.6% in the high-dose exercise group). For IL-12 and TNF-α, the percentage change was significantly higher in the low-dose (IL-12: P < .001; and TNF-α: P = .01) and high-dose (IL-12: P < .001; and TNF-α: P < .001) exercise groups compared with the control group.

Conclusions: Moderate to vigorous aerobic exercise appeared to increase levels of proinflammatory biomarkers in a dose-dependent manner in a population of healthy women at high risk of developing breast cancer. The results of the current study suggest that for healthy premenopausal women, the mechanism of reduced breast cancer risk observed in physically active individuals may not be a result of reduced levels of inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952574PMC
January 2020

Radiomics features of the primary tumor fail to improve prediction of overall survival in large cohorts of CT- and PET-imaged head and neck cancer patients.

PLoS One 2019 19;14(9):e0222509. Epub 2019 Sep 19.

Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables-HPV status and tumor volume-were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222509PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752873PMC
March 2020

Effects of alterations in positron emission tomography imaging parameters on radiomics features.

PLoS One 2019 5;14(9):e0221877. Epub 2019 Sep 5.

Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Radiomics studies require large patient cohorts, which often include patients imaged using different imaging protocols. We aimed to determine the impact of variability in imaging protocol parameters and interscanner variability using a phantom that produced feature values similar to those of patients. Positron emission tomography (PET) scans of a Hoffman brain phantom were acquired on GE Discovery 710, Siemens mCT, and Philips Vereos scanners. A standard-protocol scan was acquired on each machine, and then each parameter that could be changed was altered individually. The phantom was contoured with 10 regions of interest (ROIs). Values for 45 features with 2 different preprocessing techniques were extracted for each image. To determine the impact of each parameter on the reliability of each radiomics feature, the intraclass correlation coefficient (ICC) was calculated with the ROIs as the subjects and the parameter values as the raters. For interscanner comparisons, we compared the standard deviation of each radiomics feature value from the standard-protocol images to the standard deviation of the same radiomics feature from PET scans of 224 patients with non-small cell lung cancer. When the pixel size was resampled prior to feature extraction, all features had good reliability (ICC > 0.75) for the field of view and matrix size. The time per bed position had excellent reliability (ICC > 0.9) on all features. When the filter cutoff was restricted to values below 6 mm, all features had good reliability. Similarly, when subsets and iterations were restricted to reasonable values used in clinics, almost all features had good reliability. The average ratio of the standard deviation of features on the phantom scans to that of the NSCLC patient scans was 0.73 using fixed-bin-width preprocessing and 0.92 using 64-level preprocessing. Most radiomics feature values had at least good reliability when imaging protocol parameters were within clinically used ranges. However, interscanner variability was about equal to interpatient variability; therefore, caution must be used when combining patients scanned on equipment from different vendors in radiomics data sets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221877PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728031PMC
March 2020

Comparison of enhancement quantification from virtual unenhanced images to true unenhanced images in multiphase renal Dual-Energy computed tomography: A phantom study.

J Appl Clin Med Phys 2019 Aug;20(8):171-179

Department of Imaging Physics, MD Anderson Cancer Center, Houston, Texas.

Multiphase computed tomography (CT) exams are a commonly used imaging technique for the diagnosis of renal lesions and involve the acquisition of a true unenhanced (TUE) series followed by one or more postcontrast series. The difference in CT number of the mass in pre- and postcontrast images is used to quantify enhancement, which is an important criterion used for diagnosis. This study sought to assess the feasibility of replacing TUE images with virtual unenhanced (VUE) images derived from Dual-Energy CT datasets in renal CT exams. Eliminating TUE image acquisition could reduce patient dose and improve clinical efficiency. A rapid kVp-switching CT scanner was used to assess enhancement accuracy when using VUE compared to TUE images as the baseline for enhancement calculations across a wide range of clinical scenarios simulated in a phantom study. Three phantoms were constructed to simulate small, medium, and large patients, each with varying lesion size and location. Nonenhancing cystic lesions were simulated using distilled water. Intermediate (10-20 HU [Hounsfield units]) and positively enhancing masses (≥20 HU) were simulated by filling the spherical inserts in each phantom with varied levels of iodinated contrast mixed with a blood surrogate. The results were analyzed using Bayesian hierarchical models. Posterior probabilities were used to classify enhancement measured using VUE compared to TUE images as significantly less, not significantly different, or significantly higher. Enhancement measured using TUE images was considered the ground truth in this study. For simulation of nonenhancing renal lesions, enhancement values were not significantly different when using VUE versus TUE images, with posterior probabilities ranging from 0.23-0.56 across all phantom sizes and an associated specificity of 100%. However, for simulation of intermediate and positively enhancing lesions significant differences were observed, with posterior probabilities < 0.05, indicating significantly lower measured enhancement when using VUE versus TUE images. Positively enhancing masses were categorized accurately, with a sensitivity of 91.2%, when using VUE images as the baseline. For all scenarios where iodine was present, VUE-based enhancement measurements classified lesions with a sensitivity of 43.2%, a specificity of 100%, and an accuracy of 78.1%. Enhancement calculated using VUE images proved to be feasible for classifying nonenhancing and highly enhancing lesions. However, differences in measured enhancement for simulation of intermediately enhancing lesions demonstrated that replacement of TUE with VUE images may not be advisable for renal CT exams.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acm2.12685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698809PMC
August 2019

Time-resolved FRET and NMR analyses reveal selective binding of peptides containing the LC3-interacting region to ATG8 family proteins.

J Biol Chem 2019 09 30;294(38):14033-14042. Epub 2019 Jul 30.

Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania 17033

Selective autophagy sequesters cytoplasmic cargo for lysosomal degradation via the binding of autophagy receptors to Atg8 (autophagy-related 8) family proteins on the autophagic membrane. The sole yeast Atg8 gene has six mAtg8 (mammalian Atg8) homologs, including the MAP1LC3 (microtubule-associated protein-1 light chain 3) family and the GABA receptor-associated proteins. Selective autophagy receptors interact with two conserved hydrophobic pockets (termed the W-site and L-site) of mATG8 proteins through a linear motif called the LC3-interacting region (LIR) with the general composition (W/F/Y)(I/L/V). To address a lack in our knowledge regarding LIR peptide specificity toward each mATG8 homolog, here we used competitive time-resolved FRET to sensitively and quantitatively characterize the interactions between LIRs and mAtg8. We report that 14 representative LIR-containing peptides display differential binding affinities toward the mAtg8 proteins and identified the LIR domain peptide of TP53INP1 as exhibiting high affinity for all six mATG8 proteins. Using peptide truncation studies, we found that both N- and C-terminal acidic residues, as well as the C-terminal Cys residue of the TP53INP1 LIR peptide, are required for its high-affinity binding to LC3A and LC3B, whereas binding to the GABARAP subfamily proteins was facilitated by residues either N-terminal or C-terminal to the core motif. Finally, we used NMR chemical shift perturbation analysis to gain molecular insights into these findings. Collectively, our results may aid in the development of molecules that selectively disrupt specific mATG8-LIR interactions to dissect the biological roles of the six mATG8 homologs for potential therapeutic applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA119.008723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755805PMC
September 2019

Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma.

Sci Transl Med 2019 05;11(491)

Department of Lymphoma and Myeloma, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, and therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways to overcome resistance, an urgent clinical need in all relapsed/refractory cancers, remains difficult. Through genomic analyses of clinical specimens, we show that metabolic reprogramming toward oxidative phosphorylation (OXPHOS) and glutaminolysis is associated with therapeutic resistance to the Bruton's tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma (MCL), a B cell lymphoma subtype with poor clinical outcomes. Inhibition of OXPHOS with a clinically applicable small molecule, IACS-010759, which targets complex I of the mitochondrial electron transport chain, results in marked growth inhibition in vitro and in vivo in ibrutinib-resistant patient-derived cancer models. This work suggests that targeting metabolic pathways to subvert therapeutic resistance is a clinically viable approach to treat highly refractory malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aau1167DOI Listing
May 2019

Acupuncture for Hot Flashes in Cancer Patients: Clinical Characteristics and Traditional Chinese Medicine Diagnosis as Predictors of Treatment Response.

Integr Cancer Ther 2019 Jan-Dec;18:1534735419848494

1 University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Acupuncture is a recognized integrative modality for managing hot flashes. However, data regarding predictors for response to acupuncture in cancer patients experiencing hot flashes are limited. We explored associations between patient characteristics, including traditional Chinese medicine (TCM) diagnosis, and treatment response among cancer patients who received acupuncture for management of hot flashes.

Methods: We reviewed acupuncture records of cancer outpatients with the primary reason for referral listed as hot flashes who were treated from March 2016 to April 2018. Treatment response was assessed using the hot flashes score within a modified Edmonton Symptom Assessment Scale (0-10 scale) administered immediately before and after each acupuncture treatment. Correlations between TCM diagnosis, individual patient characteristics, and treatment response were analyzed.

Results: The final analysis included 558 acupuncture records (151 patients). The majority of patients were female (90%), and 66% had breast cancer. The median treatment response was a 25% reduction in the hot flashes score. The most frequent TCM diagnosis was qi stagnation (80%) followed by blood stagnation (57%). Older age ( P = .018), patient self-reported anxiety level ( P = .056), and presence of damp accumulation in TCM diagnosis ( P = .047) were correlated with greater hot flashes score reduction.

Conclusions: TCM diagnosis and other patient characteristics were predictors of treatment response to acupuncture for hot flashes in cancer patients. Future research is needed to further explore predictors that could help tailor acupuncture treatments for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1534735419848494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501481PMC
December 2019

Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis.

JAMA Oncol 2019 Jul;5(7):1008-1019

Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston.

Importance: Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.

Objective: To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.

Data Sources: PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.

Study Selection: Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.

Data Extraction And Synthesis: Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.

Main Outcomes And Measures: Incidences of treatment-related adverse events and differences between different drugs and cancer types.

Results: This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).

Conclusions And Relevance: Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2019.0393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487913PMC
July 2019

Impact of serious mental illness on the treatment and mortality of older patients with locoregional high-grade (nonmetastatic) prostate cancer: retrospective cohort analysis of 49 985 SEER-Medicare patients diagnosed between 2006 and 2013.

Cancer Med 2019 05 3;8(5):2612-2622. Epub 2019 Apr 3.

MD Andersen Cancer Center, University of Texas, Houston, Texas.

Background: The influence of serious mental illness (SMI) on the treatment and survival of patients with high-grade prostate cancer is not well understood. We compared the initial cancer treatment and cancer-specific mortality of SEER-Medicare patients with locoregional high-grade (nonmetastatic) prostate cancer with and without preexisting SMI.

Methods: We identified SEER-Medicare patients who were 67 years of age or older diagnosed between 2006 and 2013 with locoregional high-grade (nonmetastatic) prostate cancer. Preexisting SMI was identified by claims indicative of bipolar disorder, schizophrenia, and other psychotic disorder, during the 2 years before cancer diagnosis. We used multivariable binary logistic regression to examine associations between SMI and receipt of surgery or radiation concurrent with hormone therapy (definitive initial treatment) within 1 year after cancer diagnosis. We used Kaplan-Meier survival curves, as well as Cox proportional hazards and competing risk models to evaluate unadjusted and adjusted associations between SMI and 5-year cancer-specific survival.

Results: Among 49 985 patients with locoregional high-grade (nonmetastatic) prostate cancer, 523 (1.1%) had SMI and 49 462 (98.9%) had no SMI. Overall, SMI was associated with reduced odds of receiving surgery (OR = 0.66, 95% CI: 0.49-0.89) or radiation concurrent with hormone therapy (OR = 0.81, 95% CI: 0.67-0.98) as initial treatments in the year after cancer diagnosis. Additionally, SMI was associated with higher hazard of 5-year cancer-specific death (HR = 1.41, 95% CI: 1.06-1.89) after accounting for competing risks of non-cancer death.

Conclusion: Among SEER-Medicare patients with locoregional high-grade (nonmetastatic) prostate cancer, those with preexisting SMI-relative to those without these conditions-were less likely to receive definitive initial treatment in the year after diagnosis and had poorer cancer-specific survival 5 years after diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.2109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536920PMC
May 2019