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1.
Artículo en Inglés | MEDLINE | ID: mdl-38829958

RESUMEN

INTRODUCTION: Recent studies have identified a critical role for stromal-immune cell interactions in immunity and immune tolerance. Transcriptomic profiling has implicated stromal cells in immune-mediated disorders including the two common forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). Stromal-immune interactions may edify inflammatory state and the development of IBD-related complications such as fibrosis; yet the lack of protein markers has hampered studying stromal-immune perturbation. METHODS: In this study, we designed a 40-color spectral flow cytometry assay to characterize hematopoietic and nonhematopoietic cells in intestinal biopsies and matched blood samples from patients with CD or UC. RESULTS: We identified circulating stromal-like cells that are significantly more abundant in IBD blood samples than in healthy controls. Those cells expressed podoplanin (PDPN), a commonly used marker for fibroblasts, and they were associated with activated and memory T and B cells, and altered NK cell, monocyte, and macrophage populations. PDPN+ cells in the blood correlated with PDPN+ cells in the colon. Principal component analysis distinctly separated healthy blood samples from IBD blood samples, with stromal-like cells and B cell subtypes dominating the IBD signature; Pearson correlation detected an association between PDPN+ stromal-like cells and B cell populations in IBD blood and gut biopsies. DISCUSSION: These observations suggest that PDPN+ cells in the blood may serve as a biomarker of IBD. Understanding the relationship between stromal cells and immune cells in the intestine and the blood may provide a window into disease pathogenesis and insight into therapeutic targets for IBD.

2.
J Natl Compr Canc Netw ; 22(3): 158-166, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38626807

RESUMEN

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/epidemiología , Detección Precoz del Cáncer/métodos , Estudios Prospectivos , Predisposición Genética a la Enfermedad , Imagen por Resonancia Magnética
3.
Ann Gastroenterol ; 37(2): 206-214, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481775

RESUMEN

Background: Gastrointestinal (GI) luminal cancers can be detected at early stages by endoscopic procedures. Place-based factors, such as social deprivation and distance to specialist care, are under-investigated with regard to the stage of diagnosis. Methods: This was a retrospective cohort study among persons ≥18 years of age in the Florida Cancer Data System, a population-based cancer incidence registry. We included persons diagnosed with esophageal cancer, gastric canceror colorectal cancer, with at least 1 measure of geographic location during the period January 1, 1981, to December 31, 2016. Multivariate multinomial logistic regression was used to identify factors associated with the stage of diagnosis, including social deprivation and proximity to GI care. Results: Among 379,054 persons, the median age was 71 years, and 54% were male. Distant stage disease was significantly less likely than local stage in those of non-Hispanic/Latino ethnicity (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.89-0.94, P<0.001). Distant disease was more likely in African Americans (OR 1.30, 95%CI 1.26-1.34) and Asians (OR 1.41, 95%CI 1.27-1.56, P<0.001), with each 5-min increase in travel time to specialists, (OR 1.02, 95%CI 1.01-1.02, P<0.001), and with each 10-point increase in Social Deprivation Index (OR 1.01, 95%CI 1.01-1.02, P<0.001). Conclusions: A greater distance from care and living in areas with increased deprivation are associated with an advanced stage of diagnosis and should be recipients of policy-driven efforts to improve access to care. That the strongest risk factors include minority race and ethnicity underlines the complexity of healthcare disparities.

4.
ACG Case Rep J ; 11(3): e01301, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38501036

RESUMEN

In 2021, there were about 17,000 victims of human trafficking in the United States. We present a case of a 28-year-old sex trafficking victim who was forced to swallow 2 global positioning system trackers by her perpetrator. The gastroenterology team performed an upper endoscopy and retrieved 2 global positioning system devices from her antrum. Most of these victims do not disclose any history of abuse because of fear of their perpetrators. Further training and research can help to allow for recognition of these victims and potentially help them.

5.
Cancer Prev Res (Phila) ; 17(5): 209-215, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38361103

RESUMEN

The occurrence of multiple primary cancers (MPC) is thought to reflect increased cancer susceptibility in patients due to a combination of genetic and environmental factors. Here we conducted a retrospective review of 2,894 consecutive patients evaluated at a single institution and identified 31 (1.14%) individuals with a history of three or more primary cancers, then analyzed the genetic and environmental influences associated with their propensity for developing malignancies. We found that 35.5% of patients had a hereditary cancer syndrome (HCS), with high penetrance HCS in 72.7% of cases, suggesting that monogenic causes underly a significant proportion of triple primary cancer risk. Analysis of cancer frequencies found that the diagnosis of breast cancer was associated with a significantly lower likelihood of HCS, while the diagnosis of colorectal, prostate, and pancreas cancer was associated with a significantly higher likelihood of HCS. Comparison of HCS-positive and HCS-negative patients revealed similar demographic characteristics, mean age at first diagnosis, and family history of cancer. Moreover, no significant differences in lifestyle behaviors, occupational exposures, chronic health conditions, or treatment with chemotherapy and radiation were observed between HCS-positive and -negative groups, though outliers in tobacco smoking, as well as systemic treatment after both first and second primary cancers were observed. These findings indicate a robust contribution of HCS to cancer susceptibility among patients with triple primary cancers while environmental influences were less evident. This emphasizes the need for larger MPC cohorts incorporating additional genetic and environmental factors to more comprehensively characterize drivers of cancer risk. PREVENTION RELEVANCE: In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility. See related Spotlight, p. 193.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias Primarias Múltiples , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Múltiples/patología , Anciano , Adulto , Factores de Riesgo , Interacción Gen-Ambiente , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/epidemiología , Exposición a Riesgos Ambientales/efectos adversos
6.
Phys Rev E ; 108(5-1): 054605, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38115404

RESUMEN

We study particle-scale motion in sheared highly polydisperse amorphous materials, in which the largest particles are as much as ten times the size of the smallest. We find strikingly different behavior from the more commonly studied amorphous systems with low polydispersity. In particular, an analysis of the nonaffine motion of particles reveals qualitative differences between large and small particles: The smaller particles have dramatically more nonaffine motion, which is induced by the presence of the large particles. We characterize how the nonaffine motion changes from the low- to high-polydispersity regimes. We further demonstrate a quantitative way to distinguish between "large" and "small" particles in systems with broad distributions of particle sizes. A macroscopic consequence of the nonaffine motion is a decrease in the energy dissipation rate for highly polydisperse samples, which is due both to a geometric consequence of the changing jamming conditions for higher polydispersity and to the changing character of nonaffine motion.

8.
Cancer Prev Res (Phila) ; 16(6): 343-352, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37259800

RESUMEN

Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March 2022 were collected, with HRIs defined as participants enrolled in PRECEDE meeting guideline-based criteria for PDAC surveillance. Of 1,273 HRIs enrolled, 1,113 were eligible for inclusion, with 47.2% meeting familial pancreatic cancer criteria without a known pathogenic variant (PV) and the remainder having a pathogenic variant in a PDAC-risk gene (CDKN2A, STK11, PRSS1, BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, or EPCAM). Study participants were predominantly from the United States (82.7%), the most common age range at enrollment was 60-69 years (37.4%), and a non-PDAC cancer was present in 32.4%. There were racial/ethnic- and sex-based disparities among enrolled subjects, as the majority of participants were female (65.9%) and self-reported white (87.7%), with only 2.9% having Hispanic ethnicity. While more than 97% of participants consented to utilize imaging data and biosamples for research, there was no difference in rate of consent based on race/ethnicity, sex, or age, thereby demonstrating uniform participation in research activities among all subgroups after enrollment. Ensuring that diversity of HRIs in PDAC surveillance programs mirrors the communities served by participating centers is important. Substantial racial/ethnic- and sex-based disparities persist among recently enrolled HRIs undergoing PDAC surveillance, and therefore reducing these disparities will be a major focus of the PRECEDE Consortium moving forward. PREVENTION RELEVANCE: Pancreatic cancer surveillance is critical to decreasing pancreatic cancer mortality; therefore, it is important that pancreatic cancer surveillance studies enroll diverse patients. We demonstrate that substantial racial/ethnic- and sex-based disparities exist amongst enrollment in the international PRECEDE consortium, highlighting the dire need for future efforts to reduce these disparities. See related Spotlight, p. 305.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Estados Unidos , Persona de Mediana Edad , Anciano , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/epidemiología , Carcinoma Ductal Pancreático/genética , Páncreas/patología , Etnicidad , Neoplasias Pancreáticas
9.
Front Oncol ; 13: 1068110, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36865800

RESUMEN

Heterozygous, loss-of-function germline variants in ATM have been associated with an increased lifetime risk of breast, pancreas, prostate, stomach, ovarian, colorectal, and melanoma cancers. We conducted a retrospective review of thirty-one unrelated patients found to be heterozygous for a germline pathogenic variant in ATM and identified a significant proportion of patients in this cohort with cancers not currently associated with the ATM hereditary cancer syndrome, including carcinomas of the gallbladder, uterus, duodenum, kidney, and lung as well as a vascular sarcoma. A comprehensive review of the literature found 25 relevant studies where 171 individuals with a germline deleterious ATM variant have been diagnosed with the same or similar cancers. The combined data from these studies were then used to estimate the prevalence of germline ATM pathogenic variants in these cancers, which ranged between 0.45% and 2.2%. Analysis of tumor sequencing performed in large cohorts demonstrated that the frequency of deleterious somatic ATM alterations in these atypical cancers equaled or exceeded the alteration frequency in breast cancer and occurred at a significantly higher rate than in other DNA-damage response tumor suppressors, namely BRCA1 and CHEK2. Furthermore, multi-gene analysis of somatic alterations in these atypical cancers demonstrated significant co-occurrence of pathogenic alterations in ATM with BRCA1 and CHEK2, while there was significant mutual exclusivity between pathogenic alterations in ATM and TP53. This indicates that germline ATM pathogenic variants may play a role in cancer initiation and progression in these atypical ATM malignancies, potentially influencing these cancers to be driven toward DNA-damage repair deficiency and away from loss of TP53. As such, these findings provide evidence for broadening of the ATM-cancer susceptibility syndrome phenotype to improve the recognition of affected patients and provide more efficacious, germline-directed therapies.

10.
Fam Cancer ; 22(3): 307-311, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36513904

RESUMEN

Germline pathogenic variants in the tumor suppressor gene BAP1 are associated with the hereditary tumor predisposition syndrome with susceptibility to uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other cancers. Germline BAP1 pathogenic variants are rare in the non-cancer general population with an estimated carrier frequency of 1:19,898 but more common in cancer patients with a carrier frequency of 1:1299. In the following we present the first report of a family with two unique BAP1 pathogenic variants. Retrospective case report of a family with two unique pathogenic variants in BAP1. A male (proband) was referred to our ocular oncology clinic for second opinion for his multiple independent uveal melanomas at ages 65, 68 and 71. Given his personal history of squamous cell carcinoma at age 61, renal cell carcinoma at age 63, and family history of atypical meningioma, basal cell carcinoma, pancreatic and prostate cancers he was assessed for germline pathogenic variants in BAP1 through our ongoing research study. Sanger sequencing identified the American founder pathogenic variant, c.1717delC, pL573Wfs*3, that was confirmed in a clinical laboratory. Both the proband's brother and nephew tested negative for the familial variant through single site cascade genetic testing. However, based on the personal history of multiple basal cell carcinoma in the nephew and family history of pancreatic and laryngeal cancers (both not known to be associated with BAP1-TPDS), a large cancer panel testing was recommended for the nephew. His panel testing revealed a different BAP1 pathogenic variant, c.605G>A, p. Trp202*. This variant was not detected in the proband or the proband's brother. Based on the frequency of germline BAP1 variants in the cancer population, the chance of occurrence of two different BAP1 variants in a family with cancer history is 5.9 × 10-7. This case report provides support for the importance of offering large panel cascade genetic testing, rather than single site testing for only the family pathogenic variant, for all at risk family members especially when the family variant cannot explain all the cancers in the family.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Melanoma , Síndromes Neoplásicos Hereditarios , Neoplasias Cutáneas , Humanos , Masculino , Persona de Mediana Edad , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/genética , Predisposición Genética a la Enfermedad , Estudios Retrospectivos , Proteínas Supresoras de Tumor/genética , Mutación de Línea Germinal , Síndromes Neoplásicos Hereditarios/genética , Ubiquitina Tiolesterasa/genética
11.
Microbiol Spectr ; 11(1): e0247222, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36511710

RESUMEN

This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients on antiretroviral therapy compared to HIV-negative individuals. Seventy-nine specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, terminal ileum [TI] brush, TI wash, and saliva) during colonoscopy and at patient visits. Microbiome composition was characterized using 16S rRNA sequencing, and microbiome function was predicted using bioinformatics tools (PICRUSt and BugBase). Our analysis indicated that the ß-diversity of all intestinal samples (colon brush, colon wash, TI brush, and TI wash) from patients with HIV was significantly different from patients without HIV. Specifically, bacteria from genera Prevotella, Fusobacterium, and Megasphaera were more abundant in samples from HIV-positive patients. On the other hand, bacteria from genera Ruminococcus, Blautia, and Clostridium were more abundant in samples from HIV-negative patients. Additionally, HIV-positive patients had higher abundances of biofilm-forming and pathogenic bacteria. Furthermore, pathways related to translation and nucleotide metabolism were elevated in HIV-positive patients, whereas pathways related to lipid and carbohydrate metabolism were positively correlated with samples from HIV-negative patients. Our analyses further showed variations in microbiome composition in HIV-positive and negative patients by sampling site. Samples from colon wash, colon brush, and TI wash were significant between groups, while samples from TI brush and saliva were not significant. Taken together, here, we report altered intestinal microbiome composition and predicted function in patients with HIV compared to uninfected patients, though we found no changes in the oral microbiome. IMPORTANCE Over 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections. We now know that HIV interacts with the trillions of bacteria, fungi, and viruses in the human body termed the microbiome. Only a limited number of previous studies have compared variations in the oral and gastrointestinal microbiome with HIV infection. Here, we detail how the oral and gastrointestinal microbiome changes with HIV infection, having used 5 different sampling sites to gain a more comprehensive view of these changes by location. Our results show site-specific changes in the intestinal microbiome associated with HIV infection. Additionally, we show that while there were significant changes in the intestinal microbiome, there were no significant changes in the oral microbiome.


Asunto(s)
Microbioma Gastrointestinal , Infecciones por VIH , Microbiota , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , ARN Ribosómico 16S/genética , Microbioma Gastrointestinal/genética , Mucosa Intestinal/microbiología , Bacterias/genética
12.
Gastrointest Endosc ; 97(1): 2-10.e1, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36084717

RESUMEN

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper GI (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility. METHODS: Databases were queried through December 2021 to identify studies that examined upper endoscopy screening in LS using EGD. Mantel-Haenszel pooled odds ratios and 95% confidence intervals (CIs) for outcomes were constructed using a random-effects model to identify pooled odds of endoscopic findings in persons with LS. Event rates for detection of gastric and duodenal cancers, high-risk lesions, and clinically actionable findings were calculated. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Nine studies were identified with 2356 LS patients undergoing approximately 7838 EGDs. In total, 47 LS-associated UGI cancers (18 gastric and 29 duodenal cancers), 237 high-risk lesions, and 335 clinically actionable findings were identified. The pooled event rate for detection of any UGI cancer, high-risk lesions, and clinically actionable findings during screening were .9% (95% CI, .3-2.1; I2 = 89%), 4.2% (95% CI, 1.6-10.9; I2 = 98%), and 6.2% (95% CI, 2.2-16.5; I2 = 99%), respectively. There was no difference between LS-associated gene and gastric or duodenal cancer detection. CONCLUSIONS: In LS, there is evidence that endoscopic screening detects UGI cancers, precancerous lesions, and other clinically actionable findings that favor its use as a part of cancer risk management in LS.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Duodenales , Lesiones Precancerosas , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Detección Precoz del Cáncer , Endoscopía Gastrointestinal , Lesiones Precancerosas/diagnóstico
13.
J Crohns Colitis ; 16(11): 1687-1695, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-35642747

RESUMEN

BACKGROUND AND AIMS: The efficacy of current biologics may be limited by targeting only one pathway. Pentoxifylline [PTX] interferes with tumour necrosis factor [TNF] gene expression. We performed a randomised, placebo-controlled pilot study to determine if PTX plus vedolizumab [VDZ] in patients with Crohn's disease [CD] is safe and improves response compared with VDZ monotherapy. METHODS: Thirty adult patients with active CD were randomised to VDZ/PTX or VDZ/placebo and followed for 24 weeks. Endoscopic activity and inflammatory cytokines were measured at baseline and Week 24. Descriptive statistics were used to determine estimates of effect. RESULTS: Demographics were similar but baseline disease activity was higher in the VDZ/PTX group. There was no difference in clinical remission at Week 14 (60.0% vs 66.67%, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.16, 3.51) or steroid-free clinical remission at Week 24 in patients receiving VDZ/PTX. Improved clinical response was noted in the VDZ/PTX group at Weeks 6, 14, and 24 [Week 6: 20% vs 6.67%, Week 14: 26.67% vs 6.67%, Week 24: 40% vs 20%]. The rate of endoscopic remission was similar between the groups [40% vs 33.33%], with a greater mean decrease in Simple Endoscopic Score-CD [SES-CD] and C-reactive protein [CRP] with VDZ/PTX [SES-CD -3.17 vs -0.15, CRP -5.56 vs 0.46]. An increase in serum TNF-α concentration was observed with VDZ/placebo group; PTX mitigated this effect. No serious adverse events occurred. CONCLUSIONS: VDZ/PTX did not provide benefit over VDZ monotherapy in clinical or endoscopic remission but appeared to improve clinical response and was safe. These data should inform a fully powered study.


Asunto(s)
Enfermedad de Crohn , Pentoxifilina , Adulto , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/inducido químicamente , Fármacos Gastrointestinales , Pentoxifilina/efectos adversos , Proyectos Piloto , Inducción de Remisión , Proteína C-Reactiva , Resultado del Tratamiento
14.
Gastroenterology ; 163(2): 437-448.e1, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35483444

RESUMEN

BACKGROUND & AIMS: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. METHODS: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. RESULTS: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality. CONCLUSIONS: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.


Asunto(s)
Neoplasias del Colon , Neoplasias Gastrointestinales , Detección Precoz del Cáncer , Humanos , Modelos Lineales , Población Rural , Estados Unidos/epidemiología
16.
Soft Matter ; 18(11): 2168-2175, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35212696

RESUMEN

In development and homeostasis, multi-cellular systems exhibit spatial and temporal heterogeneity in their biochemical and mechanical properties. Nevertheless, it remains unclear how spatiotemporally heterogeneous forces affect the dynamical and mechanical properties of confluent tissue. To address this question, we study the dynamical behavior of the two-dimensional cellular vertex model for epithelial monolayers in the presence of fluctuating cell-cell interfacial tensions, which is a biologically relevant source of mechanical spatiotemporal heterogeneity. In particular, we investigate the effects of the amplitude and persistence time of fluctuating tension on the tissue dynamics. We unexpectedly find that the long-time diffusion constant describing cell rearrangements depends non-monotonically on the persistence time, while it increases monotonically as the amplitude increases. Our analysis indicates that at low and intermediate persistence times tension fluctuations drive motion of vertices and promote cell rearrangements, while at the highest persistence times the tension in the network evolves so slowly that rearrangements become rare.


Asunto(s)
Modelos Biológicos , Fenómenos Físicos
18.
Dig Dis Sci ; 67(8): 3890-3903, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34554365

RESUMEN

BACKGROUND: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM: To determine the association between immunosuppressive therapy and CDI outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Adulto , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Hospitalización , Humanos , Terapia de Inmunosupresión , Factores de Riesgo
19.
Leuk Lymphoma ; 63(5): 1160-1166, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34927537

RESUMEN

Colon extranodal marginal zone lymphoma (EMZL) is poorly characterized in the literature. We performed a retrospective review of patients with colon EMZL at our institution and from the Surveillance Epidemiology and End Results (SEER) database. Eight patients were identified in our institution with majority (88%) presenting with stage-I disease. Initial management included active surveillance, polypectomy followed by surveillance, and surgical resection followed by chemotherapy. One patient with concurrent prostate carcinoma received radiation to the rectum. Initial therapy led to complete remission in five out of six treated patients with four of them maintaining remission at 88 months. SEER database identified 361 patients with stage-I colon EMZL. Overall survival for this cohort was 73.9% at 10 years with no significant difference in outcomes between treatment groups. Our single institution experience and the SEER data analysis emphasize indolent nature of colon EMZL and need for non-aggressive therapeutic approaches.


Asunto(s)
Linfoma de Células B de la Zona Marginal , Estudios de Cohortes , Colon/patología , Humanos , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/terapia , Masculino , Pronóstico , Estudios Retrospectivos
20.
BMJ Open ; 12(9): e061465, 2022 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-36691178

RESUMEN

OBJECTIVES: To examine the sociodemographic characteristics, activities, motivations, experiences, skills and challenges of patient partners working across multiple health system settings in Canada. DESIGN: Online cross-sectional survey of self-identified patient partners. SETTING: Patient partners in multiple jurisdictions and health system organisations. PARTICIPANTS: 603 patient partners who had drawn on their experiences with the health system as a patient, family member or informal caregiver to try to improve it in some way, through their involvement in the activities of a group, organisation or government. RESULTS: Survey respondents predominantly identified as female (76.6%), white (84%) and university educated (70.2%) but were a heterogeneous group in the scope (activities and organisations), intensity (number of hours) and longevity (number of years) of their role. Primary motivations for becoming a patient partner were the desire to improve the health system based on either a negative (36.2%) or positive (23.3%) experience. Respondents reported feeling enthusiastic (83.6%), valued (76.9%) and needed (63.3%) always or most of the time; just under half felt they had always or often been adequately compensated in their role. Knowledge of the health system and the organisation they partner with are key skills needed. Two-thirds faced barriers in their role with over half identifying power imbalances. Less than half were able to see how their input was reflected in decisions or changes always or most of the time, and 40.3% had thought about quitting. CONCLUSIONS: This survey is the first of its kind to examine at a population level, the characteristics, experiences and dynamics of a large sample of self-identified patient partners. Patient partners in this sample are a sociodemographically homogenous group, yet heterogeneous in the scope, intensity and longevity of roles. Our findings provide key insights at a critical time, to inform the future of patient partnership in health systems.


Asunto(s)
Familia , Pacientes , Humanos , Femenino , Estudios Transversales , Canadá , Solución de Problemas
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