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Background: Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE. Objective: To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units. (ICUs). Design: Prospective ecologic study. Setting: 126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999. Patients: All patients admitted to participating ICUs. Measurements: Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures. Results: Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P Conclusion: Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs.

The reasons why black women are more likely to die of uterine cancer than white women do not appear to relate solely to socioeconomic factors. A total of 130 black women with uterine cancer residing in three cities between 1985 and 1987 were matched to a sample of 329 white women with uterine cancer by age and city of residence. Seventy-five percent of the black women had stage I or II disease, the mildest forms, compared with 91% of the white women. Conversely, over 11% of the black women had stage IV disease versus 3% of the white women. Black women tended to be poorer, less educated, and less likely to have a private physician or private insurance. However, black women were also more likely to have more aggressive types of cancer. When this was factored in, the excess risk of diagnosis with advanced disease among black women fell from three-and-one-quarter times the risk to twice the risk.

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, ATMwas 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.

Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P= .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2Bmutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2compared with low Ki-67 (<50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.

•Disruption of medical visits occurred among children during the first half of 2021.•COVID-19 affected non-White children and families with lower income.•COVID-19 affected children whose mother had less than a college education.•Efforts are needed by healthcare providers to make catch-up vaccination a priority.

Introduction- Patients (pts) with mantle cell lymphoma (MCL) with blastoid (B-MCL) and pleomorphic (P-MCL) histology are traditionally considered as high risk; however, there is a paucity of information regarding the differences between P-MCL and B-MCL compared to classic MCL (C-MCL) histology. In this study, we present a comprehensive genomic and transcriptomic portrait of B-MCL and P-MCL.

Background -We reported the efficacy and safety of using a combination of ibrutinib plus rituximab (IR) induction followed by short course (4 cycles) of R-HCVAD/MTX-ara-C as consolidation in previously untreated young (age ≤ 65 years)patients (pts) with mantle cell lymphoma (MCL), Wang M et al Lancet Oncology 2022. Here we report the long term follow up of this study.

Background: Mantle cell lymphoma (MCL) patients usually require immediate therapy, however about 20% of newly diagnosed MCL patients can be initially observed. A subgroup of patients who are suitable for initial observation but exhibit high-risk features are of particular concern as they have a propensity to progress. We consider these patients as high-risk smoldering MCL (defined below). Generally, these patients are observed without systemic therapy for 18-24 months. We investigated the impact of single-agent ibrutinib on time to progression for these patients who would otherwise be observed.

Introduction- Previously, our group reported results from ibrutinib with rituximab in older mantle cell lymphoma (MCL) patients (pts) with an atrial fibrillation rate of 22%. To develop a chemotherapy-free combination for elderly MCL pts, we designed this phase II clinical trial to investigate the efficacy and safety of acalabrutinib with rituximab (AR) as a first line approach in MCL pts (≥ 65 yrs).

I find Eugene McCarraher's article devoid of Christian charity toward 'suburban Catholics' who, though working hard to keep the faith once delivered to the saints, face challenges from a wider [...]

Heartbreaking Illusions Expect the unexpected when Zeljko Ivanek's Tom strolls onto the Wingfield's fire-escape landing in the Roundabout Theatre Company of New York's production of The Glass Menagerie this fall. [...]

Sitting in the Citicorp gallery next to Manhattan's St. Peter's Church, where she is directing five operas for the multicultural Magic Circle Opera Repertory Company, Alaskan-born theatre artist Jane Lind [...]

Wang: Beijing Medical Award Foundation: Honoraria; Lu Daopei Medical Group: Honoraria; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; Loxo Oncology: Consultancy, Research Funding; Targeted Oncology: Honoraria; OMI: Honoraria, Other: Travel, accommodation, expenses; Nobel Insights: Consultancy; Guidepoint Global: Consultancy; Dava Oncology: Honoraria; Verastem: Research Funding; Molecular Templates: Research Funding; OncLive: Honoraria; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding; InnoCare: Consultancy; MoreHealth: Consultancy; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding.

Background -Older patients (pts) with mantle cell lymphoma (MCL) may exhibit poor functional status and become ineligible for intensive chemo-immunotherapy or stem cell transplantation. The advent of chemotherapy-free therapies are a significant advance in MCL. We investigated the safety and efficacy of combining ibrutinib and rituximab (IR) in previously untreated older pts (age ≥65 years) with MCL in a single center, phase II clinical trial.

Background -We investigated the efficacy and safety of using a combination of ibrutinib plus rituximab (IR) followed by short course (4 cycles) of R-HCVAD/MTX-ara-C as consolidation in previously untreated young (age ≤ 65 years) patients (pts) with mantle cell lymphoma (MCL). Using a chemo-free induction may reduce the toxicities, complications and the risk of second cancers which were observed with intensive chemoimmunotherapy regimen in MCL pts.

Lee: Seattle Genetics: Research Funding; Takeda: Research Funding; Aptitude Health: Speakers Bureau; Oncternal Therapeutics: Research Funding; Guidepoint Blogal: Consultancy; Celgene: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Vega:NCI: Research Funding. Flowers:Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding; OptumRx: Consultancy; TG Therapeutics: Research Funding; BeiGene: Consultancy; Denovo Biopharma: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Kite: Research Funding; Bayer: Consultancy. Wang:Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Beijing Medical Award Foundation: Honoraria; Dava Oncology: Honoraria; Molecular Templates: Research Funding; Verastem: Research Funding; InnoCare: Consultancy; Nobel Insights: Consultancy; OncLive: Honoraria; Loxo Oncology: Consultancy, Research Funding; MoreHealth: Consultancy; Oncternal: Consultancy, Research Funding; Targeted Oncology: Honoraria; Acerta Pharma: Research Funding; Guidepoint Global: Consultancy; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; Lu Daopei Medical Group: Honoraria; Juno: Consultancy, Research Funding; VelosBio: Research Funding; BioInvent: Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding.

AbstractBackground and Objective:In August 2001, a cluster of MRSA skin infections was detected in a correctional facility. An investigation was conducted to determine its cause and to prevent further MRSA infections.Design:Case-control study.Setting:A 200-bed detention center.Patients:A case was defined as a detainee with a skin lesion from which MRSA was cultured from July 24 through December 31, 2001. Case-patients were identified by review of laboratory culture results and by skin lesion screening through point-prevalence survey and admission examination. Controls were randomly selected from an alphabetized list of detainees.Intervention:Medical staff implemented measures to improve skin disease screening, personal hygiene, wound care, and antimicrobial therapy.Results:Sixteen cases were identified: 11, 5, and 0 in the preintervention, peri-intervention, and postintervention periods, respectively. Seven case-patients and 19 controls were included in the case-control study. On multivariable analysis, working as a dormitory orderly (OR, 9.8; CI95, 0.74-638; P= .10) and a stay of longer than 36 days (OR, 6.9; CI95, 0.65-128.2; P= .14) were the strongest predictors for MRSA skin infection. The preintervention, peri-intervention, and postintervention MRSA infection rates were 11.6, 8.8, and 0 per 10,000 detainee-days, respectively. The rate of MRSA skin infections declined significantly between both the preintervention and peri-intervention periods and the postintervention period (P< .01 for both comparisons).Conclusions:MRSA skin disease can become an emergent problem in a correctional facility. Interventions targeted at skin disease screening, appropriate antimicrobial treatment, and hygiene may decrease the risk of acquiring MRSA infection in correctional facilities.

Although persons with hemophilia are known to be at increased risk of death, no studies have examined the source of medical care and other personal characteristics for associations with mortality. To determine death rates and to identify causes of death and predictors of mortality, we studied a cohort comprised of all hemophilic males identified by a six-state surveillance system. Data were obtained by medical record review of contacts with physicians, hemophilia treatment centers (HTCs), and other sources of care during 1993-1995 and from death certificates. Factors examined included age, race, state of residence, health insurance type, medical care source, hemophilia type/severity, presence of inhibitor, liver disease, HIV infection, and AIDS. A total of 2950 subjects were followed for an average of 2.6 years. Their median age was 22 years; 73% were white, 79% had hemophilia A, 42% had severe disease, and 67% had visited an HTC. During 7575 person years (PYs) of observation, 236 persons died—an age-adjusted mortality rate of 40.4 deaths/1000 PYs; 65% of deaths were HIV related. In addition to age, factors independently associated with increased risk of death (relative risk, P value) were the following: AIDS (33.5, <.001); HIV infection (4.7, <.001); liver disease (2.4, <.001); and Medicare/Medicaid insurance (1.4, .01). Those persons who had received care in an HTC had a significantly decreased risk of death (0.6, .002). Although HIV infection and the presence of severe liver disease remain strong predictors of mortality, survival is significantly greater among hemophilics who receive medical care in HTCs.

Background -The tumor microenvironment (TME) plays a vital role in the growth and survival of mantle cell lymphoma (MCL) cells. However, characterization of the TME transcriptomic profile in MCL, its prognostic impact and response to Bruton's tyrosine kinase inhibitors (BTKi) is unknown. Unlike other lymphomas, the TME in MCL patients has not been fully characterized at the transcriptomic and genomic levels. To further understand the relevance of tumor-immune landscape in tissue microenvironments in the context of BTKi, we performed multi-omic profiling of the TME in tissues from MCL patients.

Background- The WINDOW-1 regimen introduced first-line ibrutinib with rituximab (IR) followed by 4 cycles of R-HCVAD for younger mantle cell lymphoma (MCL) patients (pts) demonstrating 90% CR on IR alone and we aimed to improve the CR rate with the addition of venetoclax. We therefore investigated the efficacy and safety of IR and venetoclax (IRV) followed by risk-stratified observation or short course R-HCVAD/MTX-ARA-C as consolidation in previously untreated young patients with mantle cell lymphoma (MCL). Our aim was to use a triplet chemotherapy-free induction to reduce the toxicity, complications and minimize chemotherapy exposure in MCL pts.

To identify factors that explain a lower survival rate among black women with endometrial cancer when compared to white women.

Black women with endometrial cancer have more advanced disease and less favorable tumor grade than do white women. This study evaluated whether racial differences in tumor grade could be explained by hormone-related factors and other putative determinants of grade. Subjects included 207 white and 81 black postmenopausal women diagnosed with primary cancer of the uterine corpus between 1985 and 1987. Blacks had poorer tumor grade than whites (odds ratio for FIGO grade 2 versus grade 1 is 1.8; odds ratio for grade 3 versus grade 1 is 2.8). Over 75% of the excess of poorly differentiated tumors versus well-differentiated tumors among blacks could be explained by racial differences in use of replacement estrogens, age at first pregnancy, history of oophorectomy, poverty, stage of disease, use of screening, and access to health care. The most prominent factor was estrogen therapy, which was associated with favorable tumor grade and was used much less frequently by blacks. Although not statistically significant, a moderate racial difference in tumor grade remained after control of the potential explanatory variables. This may reflect true biologic variation between blacks and whites and may explain, in part, the observation that blacks with endometrial cancer have a worse prognosis. Copyright 1995, 1999 Academic Press

Epidemiologic evidence on the relation between nutrition and endometrial cancer (EC) is reviewed. Obesity is an important determinant of EC, probably because of its effect on the hormonal milieu of both pre-and postmenopausal women. However, epidemiologic studies of body fat distribution and EC are inconsistent, as are the data pertaining to the relation between body fat distribution and sex hormones. Randomized and observational studies of diet and sex hormones indicate that low fat diets may be associated weakly with decreased estrogen levels, and thus a lowering of EC risk. Only ecologic and case-control studies of diet and EC have been reported. These finding as well as the methodologic limitations of these study designs are discussed. Both types of studies implicate fat as a potential risk factor, while the case-control studies suggest that carotene may lower risk of EC. Epidemiologic studies of alcohol and EC also are inconsistent, but generally indicate no association, or a weak protective effect. The role of diet in the etiology of EC is unresolved. The conduct of cohort and intervention studies, which can avoid many of the methodologic shortcomings of ecologic and case-control studies, would improve our understanding of diet and EC.

A longitudinally linked data set for Georgia was used to identify characteristics, including previous prenatal care use and complications at the first birth, associated with prenatal care use in the second pregnancy among 8,224 African‐American women. More than 70% of the women who were <25 years of age at their first birth (younger women) and almost 40% of women who were ≥25 years at their first birth received inadequate care with at least one of their first two births. Women who received inadequate care in their first pregnancy were more likely to receive inadequate care in their second pregnancy than women who received adequate care in their first pregnancy. Younger women with a history of a stillbirth, neonatal death, or vacuum extraction were less likely to receive inadequate care in their subsequent pregnancy. Although this study was not able to evaluate the content of prenatal care, it suggested that many African‐American women may not receive sufficient care to prevent adverse pregnancy outcomes. Women who receive inadequate care in their first pregnancy must be targeted for interventions that help them overcome economic, situational, or attitudinal barriers to receiving adequate care in their next pregnancy.

Wang: Oncternal: Consultancy, Research Funding; Lu Daopei Medical Group: Honoraria; Juno: Consultancy, Research Funding; Guidepoint Global: Consultancy; Dava Oncology: Honoraria; MoreHealth: Consultancy; Targeted Oncology: Honoraria; Beijing Medical Award Foundation: Honoraria; Verastem: Research Funding; OncLive: Honoraria; Acerta Pharma: Research Funding; VelosBio: Research Funding; Molecular Templates: Research Funding; Nobel Insights: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; Loxo Oncology: Consultancy, Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; BioInvent: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; InnoCare: Consultancy.

Background:Complex genetic, epigenetic alterations and metabolic reprogramming are among the hallmarks of mantle cell lymphoma, an aggressive B-cell type of non-Hodgkin's lymphoma. CDKN2Aand MTAPare frequently co-deleted in human cancers including MCL. Deletion of MTAPgene results in the accumulation of methylthioadenosine (MTA), a selective inhibitor of protein arginine methyltransferase 5 (PRMT5), signifying a dependence of MTAPdeleted tumors on PRMT5. PRMT5 plays an important role in normal cellular processes viaepigenetic and post-translational modification of RNA splicing, DNA repair and cell cycle regulators. These pathways may be activated in response to targeted therapies to maintain tumor growth and survive chemotherapy. Sustained PRMT5 expression and activity could be therapeutically targeted in MTAP-deficient MCL. Mutations in RNA splicing factors are common in lymphoma and increase the susceptibility to perturbations in splicing events. Deregulated PRMT5 might induce alternative splicing, leading to loss of expression of proteins or epitopes, and subsequent immune evasion and failure of tumor specific immune therapy. Multiple mechanisms may co-exist.

Introduction

Introduction:Mantle cell lymphoma (MCL) patients (pts) who progress after ibrutinib and other lines of treatment “ultra-refractory MCL” have poor outcomes and exhibit BTK mutations infrequently (Jain P et al BJH 2018, Martin P et al Blood 2016). Venetoclax has shown promising efficacy in Phase I trial in NHL (Davids M et al JCO 2017) and is now under trials in MCL. Venetoclax response in pts with MCL after progression on ibrutinib was reported (Eyre T et al Haematologica 2018), however, genomic alterations associated with venetoclax resistance are not described. We present our experience in 24 pts with MCL treated with venetoclax and report their mutation profiles associated with progression on venetoclax.

The article announces that Jon Lien has received the Order of Canada award from Governor General Michaelle Jean.

Presents several letters to the editor regarding previously published articles. Reaction to singer Britney Spears' engagement to Kevin Federline; Thoughts on outsourcing of jobs in the U.S.

Reports on the public showing of the play `The Last Enemy,' by Jim Mirrione on the Israeli-Arab conflict in New York. Plot of the drama; Role of George White, chief executive officer of the O'Neill Theater Center in Connecticut, in the showing of the play.

Talks about the use of Scotch tape in the Improbable Theatre Company's performance of `70 Hill Lane.' Actor/director Phelim McDermott's reason for choosing the material for his play; Beguiling series of narratives woven by McDermott in the play.