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  • Type II Achalasia Is Increasing in Prevalence. Digestive diseases and sciences Zhou, M. J., Kamal, A., Freedberg, D. E., Markowitz, D., Clarke, J. O., Jodorkovsky, D. 2020

    Abstract

    BACKGROUND: Three manometric subtypes of achalasia were defined in the Chicago Classification approximately 10years ago: type I (aperistalsis), type II (pan-pressurization), and type III (spastic). Since the widespread use of this classification scheme, the evolving prevalence of these subtypes has not been elucidated. We aim to determine the prevalence of each subtype a decade after the adoption of the Chicago Classification.METHODS: This is a retrospective cohort analysis of patients diagnosed with achalasia on high-resolution manometry (HRM) at two major academic medical centers between 2015 and 2018. Patients were excluded if they had a diagnosis of another esophageal motility disorder, previously treated achalasia, or foregut surgery. Demographic data, manometric subtype, and esophageal dilatation grade on endoscopy were obtained. Prevalence of achalasia subtypes was compared with a published historical control population (2004-2007). Fischer's exact and t tests were used for analysis.RESULTS: Of 147 patients in the contemporary cohort and 99 in the historical control cohort, the prevalence of type I achalasia was 8% versus 21%, type II 63% versus 50%, and type III 29% versus 29%, respectively (p=0.01). The mean age in our population was 58years compared to 57years in the historical control, and the proportion of men 48% versus 47%, respectively (p=0.78). Mean endoscopic dilatation grade in the contemporary cohort was 1.5 for type I patients, 0.9 for type II, and 0.4 for type III, compared with 1.5, 0.6, and 0.4, respectively. Overall mean dilatation grade was 0.8 in our cohort versus 0.7 in the historical control (p=0.58).CONCLUSION: The prevalence of type II achalasia was significantly greater and prevalence of type I significantly less in our patient population compared to our predefined historical control. Other characteristics such as age and sex did not appear to contribute to these differences. Histopathological evidence has suggested that type II achalasia may be an earlier form of type I; thus, the increased prevalence of type II achalasia may be related to earlier detection of the disease. The adoption of HRM, widespread use of the Chicago Classification, and increased disease awareness in the past decade may be contributing to these changes in epidemiology.

    View details for DOI 10.1007/s10620-020-06668-7

    View details for PubMedID 33089487

  • Patient and Physician Factors Associated with Adenoma and Sessile Serrated Lesion Detection Rates. Digestive diseases and sciences Zhou, M. J., Lebwohl, B. n., Krigel, A. n. 2020

    Abstract

    Sessile serrated lesions (SSLs) have been increasingly recognized as precursors to colorectal cancer. Unlike adenoma detection rate (ADR), there is currently no agreed-upon benchmark for SSL detection rate (SSLDR), and data on factors that impact SSL detection are limited. We aimed to identify patient, endoscopist, and procedural factors associated with SSL and adenoma detection.We used a single-center electronic endoscopy database to identify all patients ages ≥ 50 years who underwent outpatient screening colonoscopy from January 1, 2012, to June 30, 2018. Univariable Chi-square analysis was used to determine patient, endoscopist, and procedure-related factors associated with SSL or adenoma detection. We used logistic regression with generalized estimating equations, accounting for clustering by individual endoscopist, to determine factors independently associated with ADR and SSLDR.We identified 10,538 unique patients who underwent colonoscopy performed by 28 endoscopists. Overall SSLDR was 2.2%, and overall ADR was 29.1%. On multivariable analysis, patient age, sex, BMI, smoking, endoscopist withdrawal time, and year of colonoscopy were independent predictors of ADR. Smoking and year of colonoscopy were independent predictors of SSLDR. Sub-optimal bowel preparation was inversely associated with SSL detection but not ADR.In this large study of patients undergoing average-risk screening colonoscopy, overall SSLDR was low, indicating that methods for increasing SSLDR are needed. Our findings suggest that endoscopists may take into account risk factors for SSLs, such as smoking history, and recognize that the detection of such lesions, even more so than for adenomas, is dependent on optimal bowel preparation.

    View details for DOI 10.1007/s10620-020-06419-8

    View details for PubMedID 32564206

  • Symptoms and demographic factors associated with early-onset colorectal neoplasia among individuals undergoing diagnostic colonoscopy. European journal of gastroenterology & hepatology Krigel, A. n., Zhou, M. n., Terry, M. B., Kastrinos, F. n., Lebwohl, B. n. 2020; 32 (7): 821–26

    Abstract

    The incidence and mortality of colorectal cancer (CRC) are increasing in adults under 50 years. Risk factors associated with early-onset colorectal neoplasia (CRN) are uncertain. We aimed to identify clinical predictors associated with the presence of CRN detected by diagnostic colonoscopy in symptomatic individuals under 50 years of age.We used a single-center endoscopy database to identify symptomatic patients 18-49 years of age who underwent ambulatory colonoscopy between 2007 and 2017. Pathology reports identified CRN as adenomas, advanced adenomas (based on size or histology), or adenocarcinomas. Multivariable analysis was used to determine factors associated with CRN.We identified 4333 eligible patients of whom 363 (8.4%) had any CRN and 48 (1.1%) had advanced neoplasia (advanced adenoma or adenocarcinoma). Factors associated with any CRN on multivariable analysis included male sex [odds ratio (OR) 1.50 (1.19-1.88)], older age group [compared to 18-29 years, OR for 30-39: 3.12 (1.93-5.04); OR for 40-49: 4.68 (2.97-7.36)], obesity [OR for BMI 30-34.9 compared to 18-24.9: 1.44 (1.04-2.01)], and any tobacco use [OR 1.63 (1.18-2.23)]. Anemia was associated with advanced neoplasia [OR 3.11 (1.32-7.34)]. Of the advanced neoplastic lesions, 38 of 48 (79.2%) were located in the distal colon.In the largest study to date of symptomatic individuals under 50 years of age undergoing colonoscopy in the USA, advanced CRN was most often detected in the distal colon and was associated with anemia, but not with abnormal bowel habits or abdominal pain. We also found that patients with CRN under 50 years of age were more likely to be male, smokers, and obese. These findings should prompt further investigation of these risk factors alone and in combination.

    View details for DOI 10.1097/MEG.0000000000001720

    View details for PubMedID 32243343

  • Clinicopathologic Characteristics and Impact of Oophorectomy for Ovarian Metastases from Colorectal Cancer. The oncologist Ursem, C. n., Zhou, M. n., Paciorek, A. n., Atreya, C. E., Ko, A. H., Venook, A. n., Zhang, L. n., Van Loon, K. n. 2020; 25 (7): 564–71

    Abstract

    As survival with metastatic colorectal cancer (CRC) and imaging modalities improve, detection of ovarian metastases may be increasing. The ovary may serve as a sanctuary site for malignant cells; however, there is a paucity of data regarding the role for oophorectomy.This is a single-institution retrospective study of patients with CRC with ovarian metastases from 2009 to 2017. We evaluated patient, disease, and treatment related factors associated with overall survival (OS) from initial diagnosis of metastatic CRC.Of 108 patients assessed, the median age was 50, 19% had localized disease at initial presentation, 64% had ovarian metastases at initial CRC diagnosis, and 77% underwent oophorectomy. Median OS was 29.6 months across all patients, and it was 36.7 months in patients who underwent oophorectomy versus 25.0 months in patients who did not (hazard ratio [HR] 0.54). In multivariate analysis, the effect of oophorectomy on OS suggested protection but was not statistically significant (HR 0.57). Resection of primary tumor was performed in 71% of patients, which was independently associated with improved OS (HR 0.21). Twelve patients (11%) remained alive at 5 years after diagnosis of metastatic disease.Although it has been previously reported that patients with CRC with ovarian metastases have poor prognosis, the median OS for this cohort was comparable to existing OS data for patients with metastatic CRC. In patients treated with chemotherapy, we did not find the ovarian metastasis to frequently serve as a sanctuary site of disease. However, we found that in carefully selected patients, oophorectomy may confer a survival benefit.In colorectal cancer (CRC) ovarian metastasis is not necessarily associated with worse prognosis than metastasis to other sites. In carefully selected patients with ovarian metastases from CRC, oophorectomy may confer a survival benefit. Specifically, development of ovarian metastasis early in the disease course, resection of the primary tumor, and limited extraovarian metastatic disease are clinical features that are potentially associated with benefit from oophorectomy. A subset of patients with ovarian metastasis from CRC have potential to become long-term survivors (>5 years).

    View details for DOI 10.1634/theoncologist.2019-0282

    View details for PubMedID 32031306

  • The local hospital milieu and healthcare-associated vancomycin-resistant enterococcus acquisition. The Journal of hospital infection Zhou, M. J., Li, J. n., Salmasian, H. n., Zachariah, P. n., Yang, Y. X., Freedberg, D. E. 2019; 101 (1): 69–75

    Abstract

    Vancomycin-resistant enterococcus (VRE) causes 4% of all healthcare-associated infections in the USA. The process by which the local hospital milieu contributes to VRE acquisition is not fully understood.To determine the importance of specific factors within the local hospital environment for healthcare-associated VRE acquisition.This retrospective cohort study included patients admitted to six intensive care units at an academic medical centre from January 2012 to December 2016 with negative rectal VRE cultures on admission. VRE acquisition was defined as a positive surveillance swab performed at any time after the initial negative swab during the index hospitalization. The exposures of interest were VRE colonization pressure, VRE importation pressure, and use of vancomycin. Multivariable Cox proportional hazards modelling was performed, with patients followed until VRE acquisition, death, or for up to 30 days.Of 8485 patients who were initially VRE negative, 161 patients acquired VRE. On univariate analysis, patients with VRE acquisition were more likely to have received vancomycin, to have had a neighbouring patient who received vancomycin, to have high VRE importation pressure, or to have high VRE colonization pressure. On multivariable analysis, only high VRE colonization pressure was an independent predictor of VRE acquisition (adjusted hazard ratio: 1.79; 95% confidence interval: 1.19-2.70).VRE colonization pressure was the most important risk factor for healthcare-associated VRE acquisition, regardless of VRE importation pressure. Interventions seeking to reduce VRE acquisition should focus on minimizing transmission between patients with known VRE and the local hospital environment.

    View details for DOI 10.1016/j.jhin.2018.07.018

    View details for PubMedID 30026006

    View details for PubMedCentralID PMC6309650

  • Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection. Intensive care medicine Freedberg, D. E., Zhou, M. J., Cohen, M. E., Annavajhala, M. K., Khan, S. n., Moscoso, D. I., Brooks, C. n., Whittier, S. n., Chong, D. H., Uhlemann, A. C., Abrams, J. A. 2018; 44 (8): 1203–11

    Abstract

    Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection.This was a prospective cohort study of medical ICU adults. Rectal surveillance swabs were performed at admission, selectively cultured for vancomycin-resistant Enterococcus (VRE), and assessed using 16S rRNA gene sequencing. Patients were followed for 30 days for death or culture-proven bacterial infection.Of 301 patients, 123 (41%) developed culture-proven infections and 76 (25%) died. Fecal biodiversity (Shannon index) did not differ based on death or infection (p = 0.49). The presence of specific pathogens at ICU admission was associated with subsequent infection with the same organism for Escherichia coli, Pseudomonas spp., Klebsiella spp., and Clostridium difficile, and VRE at admission was associated with subsequent Enterococcus infection. In a multivariable model adjusting for severity of illness, VRE colonization and Enterococcus domination (≥ 30% 16S reads) were both associated with death or all-cause infection (aHR 1.46, 95% CI 1.06-2.00 and aHR 1.47, 95% CI 1.00-2.19, respectively); among patients without VRE colonization, Enterococcus domination was associated with excess risk of death or infection (aHR 2.13, 95% CI 1.06-4.29).Enterococcus status at ICU admission was associated with risk for death or all-cause infection, and rectal carriage of common ICU pathogens predicted specific infections. The gastrointestinal microbiome may have a role in risk stratification and early diagnosis of ICU infections.

    View details for DOI 10.1007/s00134-018-5268-8

    View details for PubMedID 29936583

    View details for PubMedCentralID PMC6309661

  • Squamous cell carcinoma of unknown primary of the head and neck: Favorable prognostic factors comparable to those in oropharyngeal cancer. Head & neck Zhou, M. J., van Zante, A. n., Lazar, A. A., Groppo, E. R., Garsa, A. A., Ryan, W. R., El-Sayed, I. H., Eisele, D. W., Yom, S. S. 2018; 40 (5): 904–16

    Abstract

    Treatment for squamous cell carcinoma (SCC) of unknown primary consists of radiotherapy (RT) +/- chemotherapy or neck dissection +/- adjuvant RT/chemoradiotherapy (CRT). We compared these strategies and identified prognostic factors.From 1993 to 2015, 75 patients with SCC of unknown primary had RT-based or surgery-based treatment. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Event-time distributions were estimated using the Kaplan-Meier method.Five-year OS and DFS for RT-based and surgery-based treatments were similar (OS 73% vs 68%, respectively; DFS 65% vs 64%, respectively). Among 38 patients with p16 data, 76% were p16 positive and showed improved 5-year DFS (90% vs 33%; P = .001) and OS (96% vs 33%; P < .001). Smoking history ≤10 pack-years conferred better 5-year DFS (88% vs 49%; P < .001) and OS (91% vs 59%; P < .001).RT-based and surgery-based treatments produced similar outcomes. Patients with p16-positive disease with ≤10 pack-years of smoking history and limited nodal stage constitute a "low-risk" group in SCC of unknown primary similar to that in oropharyngeal cancer.

    View details for DOI 10.1002/hed.25028

    View details for PubMedID 29210145

  • Different outcomes for relapsed versus refractory neuroblastoma after therapy with (131)I-metaiodobenzylguanidine ((131)I-MIBG). European journal of cancer (Oxford, England : 1990) Zhou, M. J., Doral, M. Y., DuBois, S. G., Villablanca, J. G., Yanik, G. A., Matthay, K. K. 2015; 51 (16): 2465–72

    Abstract

    (131)I-metaiodobenzylguanidine ((131)I-MIBG) is a targeted radiopharmaceutical with significant activity in high-risk relapsed and chemotherapy-refractory neuroblastoma. Our primary aim was to determine if there are differences in response rates to (131)I-MIBG between patients with relapsed and treatment-refractory neuroblastoma.This was a retrospective cohort analysis of 218 patients with refractory or relapsed neuroblastoma treated with (131)I-MIBG at UCSF between 1996 and 2014. Results were obtained by chart review and database abstraction. Baseline characteristics and response rates between relapsed patients and refractory patients were compared using Fisher exact and Wilcoxon rank sum tests, and differences in overall survival (OS) were compared using the log-rank test.The response rate (complete and partial response) to (131)I-MIBG-based therapies for all patients was 27%. There was no difference in response rates between relapsed and refractory patients. However, after (131)I-MIBG, 24% of relapsed patients had progressive disease compared to only 9% of refractory patients, and 39% of relapsed patients had stable disease compared to 59% of refractory patients (p=0.02). Among all patients, the 24-month OS was 47.0% (95% confidence interval (CI) 39.9-53.9%). The 24-month OS for refractory patients was significantly higher at 65.3% (95% CI 51.8-75.9%), compared to 38.7% (95% CI 30.4-46.8%) for relapsed patients (p<0.001).Although there was no significant difference in overall response rates to (131)I-MIBG between patients with relapsed versusrefractory neuroblastoma, patients with prior relapse had higher rates of progressive disease and had lower 2-year overall survival after (131)I-MIBG compared to patients with refractory disease.

    View details for DOI 10.1016/j.ejca.2015.07.023

    View details for PubMedID 26254811

    View details for PubMedCentralID PMC4607645

  • A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors CANCER DISCOVERY Jahchan, N. S., Dudley, J. T., Mazur, P. K., Flores, N., Yang, D., Palmerton, A., Zmoos, A., Vaka, D., Tran, K. Q., Zhou, M., Krasinska, K., Riess, J. W., Neal, J. W., Khatri, P., Park, K. S., Butte, A. J., Sage, J. 2013; 3 (12): 1364-1377

    Abstract

    Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.Our work shows the power of bioinformatics-based drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel class of molecules to treat patients with SCLC, a cancer for which no effective novel systemic treatments have been identified in several decades. In addition, our experiments highlight the importance of novel autocrine mechanisms in promoting the growth of neuroendocrine tumor cells.

    View details for DOI 10.1158/2159-8290.CD-13-0183

    View details for Web of Science ID 000328257500023

    View details for PubMedID 24078773

    View details for PubMedCentralID PMC3864571

  • Walking impairment questionnaire improves mortality risk prediction models in a high-risk cohort independent of peripheral arterial disease status. Circulation. Cardiovascular quality and outcomes Nead, K. T., Zhou, M., Caceres, R. D., Olin, J. W., Cooke, J. P., Leeper, N. J. 2013; 6 (3): 255-261

    Abstract

    Background- The Walking Impairment Questionnaire (WIQ) is a subjective measure of patient-reported walking performance developed for peripheral arterial disease. The purpose of this study is to examine whether this simple tool can improve the predictive capacity of established risk models and whether the WIQ can be used in patients without peripheral arterial disease. Methods and Results- At baseline we assessed the walking distance, stair-climbing, and walking speed WIQ category scores among individuals who were undergoing coronary angiography. During a median follow-up of 5.0 years, there were 172 mortalities among 1417 study participants. Adjusted Cox proportional hazards models showed that all 3 WIQ categories independently predicted future all-cause and cardiovascular mortality, including among individuals without peripheral arterial disease (P<0.001). Compared with the cardiovascular risk factors model, we observed significantly increased risk discrimination with a C-index of 0.741 (change in C-index, 0.040; 95% confidence interval, 0.011-0.068) and 0.832 (change in C-index, 0.080; 95% confidence interval, 0.034-0.126) for all-cause and cardiovascular mortality, respectively. Examination of risk reclassification using the net reclassification improvement index showed a 48.4% (P<0.001) improvement for all-cause mortality and a 77.4% (P<0.001) improvement for cardiovascular mortality compared with the cardiovascular risk factors model. Conclusions- All 3 WIQ categories independently predicted future all-cause and cardiovascular mortality. Importantly, we found that this subjective measure of walking ability could be extended to patients without peripheral arterial disease. The addition of the WIQ scores to established cardiovascular risk models significantly improved risk discrimination and reclassification, suggesting broad clinical use for this simple, inexpensive test.

    View details for DOI 10.1161/CIRCOUTCOMES.111.000070

    View details for PubMedID 23633217

  • Usefulness of the Addition of Beta-2-Microglobulin, Cystatin C and C-Reactive Protein to an Established Risk Factors Model to Improve Mortality Risk Prediction in Patients Undergoing Coronary Angiography AMERICAN JOURNAL OF CARDIOLOGY Nead, K. T., Zhou, M. J., Caceres, R. D., Sharp, S. J., Wehner, M. R., Olin, J. W., Cooke, J. P., Leeper, N. J. 2013; 111 (6): 851-856

    Abstract

    Evidence-based therapies are available to reduce the risk for death from cardiovascular disease, yet many patients go untreated. Novel methods are needed to identify those at highest risk for cardiovascular death. In this study, the biomarkers β2-microglobulin, cystatin C, and C-reactive protein were measured at baseline in a cohort of participants who underwent coronary angiography. Adjusted Cox proportional-hazards models were used to determine whether the biomarkers predicted all-cause and cardiovascular mortality. Additionally, improvements in risk reclassification and discrimination were evaluated by calculating the net reclassification improvement, C-index, and integrated discrimination improvement with the addition of the biomarkers to a baseline model of risk factors for cardiovascular disease and death. During a median follow-up period of 5.6 years, there were 78 deaths among 470 participants. All biomarkers independently predicted future all-cause and cardiovascular mortality. A significant improvement in risk reclassification was observed for all-cause (net reclassification improvement 35.8%, p = 0.004) and cardiovascular (net reclassification improvement 61.9%, p = 0.008) mortality compared to the baseline risk factors model. Additionally, there was significantly increased risk discrimination with C-indexes of 0.777 (change in C-index 0.057, 95% confidence interval 0.016 to 0.097) and 0.826 (change in C-index 0.071, 95% confidence interval 0.010 to 0.133) for all-cause and cardiovascular mortality, respectively. Improvements in risk discrimination were further supported using the integrated discrimination improvement index. In conclusion, this study provides evidence that β2-microglobulin, cystatin C, and C-reactive protein predict mortality and improve risk reclassification and discrimination for a high-risk cohort of patients who undergo coronary angiography.

    View details for DOI 10.1016/j.amjcard.2012.11.055

    View details for Web of Science ID 000316537700013

    View details for PubMedID 23290308

    View details for PubMedCentralID PMC3594484

  • Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease JOURNAL OF VASCULAR SURGERY Leeper, N. J., Myers, J., Zhou, M., Nead, K. T., Syed, A., Kojima, Y., Caceres, R. D., Cooke, J. P. 2013; 57 (3): 728-733

    Abstract

    The objective of this study was to assess the predictive value of clinical and exercise test variables in patients with peripheral arterial disease (PAD).A customized symptom-limited ramp treadmill protocol was used to assess 725 PAD patients referred for exercise testing at the Palo Alto Veterans Hospital between 1997 and 2011. Detailed clinical and exercise test data were collected at baseline, and patients were followed up for a mean of 11.3 ± 6.3 years.During follow-up, there were 364 deaths. Baseline exercise capacity was 7.0 ± 2.6 metabolic equivalents (METs) among survivors and 5.5 ± 2.4 METs in those who died (P < .001). Although several physiologic parameters differed between survivors and nonsurvivors, age-adjusted Cox regression revealed that exercise capacity was the strongest independent predictor of death. Each additional MET achieved was associated with age-adjusted 18% and 20% reductions in all-cause and cardiovascular mortality, respectively (P < .001 for both). This variable surpassed all classical risk factors (including smoking and history of congestive heart failure) and all measured exercise test responses (including symptoms and electrocardiograph abnormalities).Among PAD patients, reduced exercise capacity is the most powerful harbinger of long-term mortality. This factor has predictive power beyond traditional risk factors and confirms the critical importance of fitness in this cohort.

    View details for DOI 10.1016/j.jvs.2012.07.051

    View details for Web of Science ID 000315944400019

    View details for PubMedID 23044259

    View details for PubMedCentralID PMC3543469

  • The Walking Impairment Questionnaire Predicts Total and Cardiovascular Mortality Independent of Peripheral Artery Disease Status Nead, K. T., Zhou, M., Diaz-Caceres, R., Roberts, S. E., Lee, W. L., Phan, N. H., Roberts, S. C., Garcia, K., Chhor, B., Luong, D. N., Cooke, J. P., Leeper, N. J. LIPPINCOTT WILLIAMS & WILKINS. 2012
  • Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease Zhou, M., Leeper, N. J., Nead, K. T., Syed, A., Abella, J., Kojima, Y., Panchal, S. N., Cooke, J. P., Myers, J. SAGE PUBLICATIONS LTD. 2012: 204–5